NAD+ vs Glutathione

NAD+ is a coenzyme that carries electrons through energy metabolism and feeds the sirtuin and PARP enzymes, while glutathione is a three-amino-acid antioxidant that neutralises oxidants and toxins directly. One is about producing and signalling energy, the other about cleaning up the oxidative by-products of that work. They meet at a single point, NADPH, which recycles spent glutathione. Here is how they compare, what the human studies on each found, and how we supply them.

Findings

• NAD+ is not a peptide. It is a dinucleotide coenzyme for redox reactions and an essential cofactor for sirtuins, CD38 and poly(ADP-ribose) polymerases (2021 review).
• Glutathione is a tripeptide, γ-L-glutamyl-L-cysteinylglycine, present in all mammalian tissues at 1 to 10 mM and the most abundant non-protein thiol in the body (2013 review).
• In a 6-month randomised, double-blind trial in 54 adults, oral glutathione raised glutathione 30 to 35% in red cells, plasma and lymphocytes at the higher dose (2015).
• In a randomised, double-blind crossover trial in healthy adults aged 55 to 79, the precursor nicotinamide riboside raised NAD+ in blood cells by about 60% over placebo (2018).

What is NAD+?

Nicotinamide adenine dinucleotide is a coenzyme found in every living cell. In its oxidised form, NAD+, it accepts electrons in the reactions that break down fuel; as NADH it hands them to the mitochondria. It is also consumed as a substrate by three enzyme families, the sirtuins, CD38 and the poly(ADP-ribose) polymerases, which link NAD+ to DNA repair, chromatin remodelling, cellular senescence and immune function (Covarrubias et al., Nat Rev Mol Cell Biol, 2021). Because those enzymes use NAD+ up, the cell has to keep remaking it. The chemistry is explained in NAD+ Is Not a Peptide.

Why NAD+ is studied

The research interest centres on decline. In 49 human pelvic skin samples from donors aged newborn to 77, NAD+ fell with age in both men and women, while activity of the NAD+-consuming PARP enzyme rose in men (Massudi et al., PLoS One, 2012). Restoring NAD+ in old or diseased animals has improved health and extended lifespan, which drove the search for NAD-boosting molecules (Rajman et al., Cell Metab, 2018).

The human research

Most human NAD+ data come from precursors. In a 2 × 6-week randomised, double-blind, placebo-controlled crossover trial, 30 healthy adults aged 55 to 79 were randomised and 24 completed; nicotinamide riboside was well tolerated and raised NAD+ in peripheral blood mononuclear cells by about 60% over placebo (Martens et al., Nat Commun, 2018). In a 10-week randomised, double-blind trial in postmenopausal women with prediabetes and overweight or obesity, nicotinamide mononucleotide increased muscle insulin sensitivity, insulin signalling and remodelling, with no change on placebo (Yoshino et al., Science, 2021).

NAD+ itself has been infused directly. In a 2019 pilot, 11 healthy men aged 30 to 55 took part (8 infused, 3 controls). During a 6-hour intravenous infusion, plasma NAD+ did not rise for the first 2 hours, as it was cleared rapidly; by 6 hours, NAD+ and its metabolites were about 400% above baseline (Grant et al., Front Aging Neurosci, 2019). The wider trial record is in NAD+ Restoration: What the Research Shows.

What is glutathione?

Glutathione (GSH) is a tripeptide built from glutamate, cysteine and glycine. It defends against oxidative stress, conjugates foreign compounds for removal, and helps regulate redox signalling, cell proliferation, immune function and fibrosis. Cells make it in the cytosol; the main limits are the supply of cysteine and the activity of glutamate cysteine ligase, the rate-limiting enzyme (Lu, Biochim Biophys Acta, 2013). When glutathione neutralises an oxidant it becomes oxidised glutathione (GSSG), which glutathione reductase converts back to GSH using NADPH, forming a redox cycle (Lu, 2013; Forman et al., Mol Aspects Med, 2009). Our overview is in Glutathione: The Research Behind the Antioxidant.

The human research

Whether glutathione taken by mouth reaches the tissues was long debated. A 6-month randomised, double-blind, placebo-controlled trial in 54 non-smoking adults settled part of it: blood glutathione rose at 1, 3 and 6 months at both doses, by 30 to 35% in erythrocytes, plasma and lymphocytes and 260% in buccal cells at the higher dose. The oxidised-to-reduced glutathione ratio fell, a sign of lower oxidative stress, and natural killer cell activity more than doubled at 3 months in the high-dose group. Levels returned to baseline after a 1-month washout (Richie et al., Eur J Nutr, 2015).

In a randomised, double-blind study of 60 healthy medical students, 4 weeks of oral glutathione lowered the skin melanin index at all six measured sites, significantly more than placebo at two of them (Arjinpathana and Asawanonda, J Dermatolog Treat, 2012). In an open-label pilot in non-alcoholic fatty liver disease, 29 patients completed 4 months of oral glutathione after 3 months of lifestyle change, and ALT, triglycerides and ferritin fell (Honda et al., BMC Gastroenterol, 2017). A 2009 double-blind pilot of intravenous glutathione in 21 people with Parkinson’s disease found it well tolerated, with no significant difference in symptom scores (Hauser et al., Mov Disord).

How do NAD+ and glutathione compare side by side?

Question	NAD+	Glutathione
What is it?	Dinucleotide coenzyme (not a peptide)	Tripeptide: glutamate, cysteine, glycine
Size	Two nucleotides joined by phosphates	3 amino acids
Main research area	Energy metabolism, ageing, sirtuin and PARP biology	Oxidative stress, detoxification, skin pigment, liver
Mechanism	Carries electrons; consumed by sirtuins, PARPs, CD38	Donates electrons to oxidants; conjugates toxins
Human evidence	Precursor RCTs (NR, NMN); one IV NAD+ pilot	Oral RCTs (body stores, skin); liver and Parkinson’s pilots
Forms we supply	500 mg vial; nasal spray (250 mg and 500 mg)	600 mg and 1500 mg vials

Where do NAD+ and glutathione connect?

The link is the recycling step. Glutathione reductase turns oxidised glutathione back into its active form using NADPH, a phosphorylated relative of NAD+ (Lu, 2013). A cell short of reducing power therefore struggles to keep its glutathione active, however much it makes. The two also respond to the same damage from opposite ends: oxidative DNA damage drives PARP activity, which consumes NAD+, and in the 2012 skin study lipid peroxidation and DNA damage correlated strongly, alongside the age-linked NAD+ decline (Massudi et al., 2012). Glutathione’s job is to limit that oxidative load in the first place.

Which one fits which research question?

• Energy metabolism, sirtuin or PARP activity, and age-related NAD+ decline: NAD+. Its literature measures NAD+ pools, insulin sensitivity and the enzymes that consume it.
• Oxidative stress markers, GSH/GSSG ratio, detoxification and skin pigmentation: glutathione, which has the controlled human studies on body stores and the melanin index.
• Liver research: glutathione has the fatty liver pilot; see also peptides for fatty liver.

Can NAD+ and glutathione be studied together?

Yes. Because one supplies the reducing power that keeps the other active, a design using both can ask whether supporting the NAD+ pool changes glutathione status, measured by the GSH/GSSG ratio. That rationale is built from each compound’s biochemistry; we found no controlled human trial of the pair. Glutathione appears with MOTS-c and SS-31 in the Mitochondrial Energy stack, and the NAD+ spray is part of the Cognitive Clarity Spray Stack. NAD+ is compared with MOTS-c in NAD+ vs MOTS-c.

How are NAD+ and glutathione supplied?

NAD+ comes as a 500 mg lyophilised vial and as a ready-mixed NAD+ Nasal Spray (0.175 mL per press) in 250 mg and 500 mg bottles. Glutathione comes as 600 mg and 1500 mg lyophilised vials. Vials are reconstituted with bacteriostatic water; see the NAD+ reconstitution guide and the glutathione reconstitution guide. Certificates of analysis are on the lab reports page, and every order ships from within Canada by Canada Post Xpresspost.

Frequently asked questions

What is the difference between NAD+ and glutathione?

NAD+ is a dinucleotide coenzyme that carries electrons in energy metabolism and fuels sirtuins and PARP enzymes. Glutathione is a three-amino-acid peptide that neutralises oxidants and conjugates toxins. NAD+ is about making and signalling energy; glutathione is about limiting oxidative damage.

Is NAD+ better than glutathione?

Neither is better in general; they answer different research questions. NAD+ research measures energy metabolism and NAD+ decline with age. Glutathione research measures oxidative stress, the GSH/GSSG ratio and, in human trials, body glutathione stores and skin pigmentation.

Does NAD+ raise glutathione?

Not directly. Glutathione reductase uses NADPH, a phosphorylated relative of NAD+, to recycle oxidised glutathione back to its active form. That biochemical link is well established, but we found no controlled human trial showing that NAD+ raises glutathione levels.

Can NAD+ and glutathione be studied together?

Yes. Because one supplies the reducing power that keeps the other active, a design using both can test whether the NAD+ pool affects glutathione status. That rationale comes from each compound’s biochemistry rather than from a combined trial.

Where can I buy NAD+ and glutathione in Canada?

Vistara Labs supplies NAD+ as a 500 mg vial and a ready-mixed nasal spray, and glutathione as 600 mg and 1500 mg vials, shipped from within Canada by Canada Post Xpresspost.

Product details from vistaralabs.ca, October 2026. Sources: Covarrubias AJ et al. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021. PMID 33353981. Massudi H et al. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012. PMID 22848760. Rajman L, Chwalek K, Sinclair DA. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metab. 2018. PMID 29514064. Martens CR et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018. PMID 29599478. Yoshino M et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021. PMID 33888596. Grant R et al. A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+. Front Aging Neurosci. 2019. PMID 31572171. Lu SC. Glutathione synthesis. Biochim Biophys Acta. 2013. PMID 22995213. Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009. PMID 18796312. Richie JP Jr et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr. 2015. PMID 24791752. Arjinpathana N, Asawanonda P. Glutathione as an oral whitening agent: a randomized, double-blind, placebo-controlled study. J Dermatolog Treat. 2012. PMID 20524875. Honda Y et al. Efficacy of glutathione for the treatment of nonalcoholic fatty liver disease: an open-label, single-arm, multicenter, pilot study. BMC Gastroenterol. 2017. PMID 28789631. Hauser RA et al. Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson’s disease. Mov Disord. 2009. PMID 19230029.

More on this: Cellular Energy & Mitochondrial Research.