Aging & Longevity

Dynamics of blood NAD and glutathione in health, disease, aging, and under NAD+-booster treatment.

TL;DR

A standardized enzymatic cycling assay workflow for measuring NAD+, NADH, NADP+, NADPH, GSH, and GSSG from a single whole-blood sample revealed that these metabolites follow a normal distribution and remain unchanged during aging in healthy adults, while high-dose nicotinic acid caused a 4-6-fold increase in blood NAD+ and distinct disease-dependent 'redox fingerprints' were observed across degenerative diseases including cancers.

Key Findings

A standardized enzymatic cycling assay workflow was developed to simultaneously quantify NAD+, NADH, NADP+, NADPH, GSH, and GSSG from a single whole-blood sample.

  • The workflow uses enzymatic cycling assays capable of measuring all six metabolites from one sample.
  • The method is described as a 'standardized workflow' suitable for use in clinical and research settings.
  • The approach was applied to a healthy population aged 18-70 years as well as to disease groups and treated individuals.

In healthy individuals aged 18-70 years, blood NAD, NADP, and glutathione metabolites follow a normal distribution and remain unchanged during aging.

  • The healthy population sampled spanned an age range of 18-70 years.
  • Metabolite levels showed a normal distribution across this population.
  • No significant age-related changes were detected in any of the six measured metabolites within this range.
  • These data establish reference (healthy) values for these metabolites in human blood.

High-dose nicotinic acid (a B3 vitamin and NAD+-booster) resulted in a 4-6-fold increase of blood NAD+ in healthy individuals.

  • The increase in blood NAD+ was 4-6-fold above baseline levels following high-dose nicotinic acid treatment.
  • The magnitude of the response varied across individuals, suggesting the need for 'personalized dosing and follow-up in treatment and drug trials.'
  • Nicotinic acid is described as one of the 'high-dose B3-vitamin forms, so-called NAD+-boosters.'
  • The variable response highlights that population-level dosing without monitoring may be inadequate.

Different degenerative diseases, including cancers, exhibit distinct disease-dependent 'redox fingerprints' of NAD and glutathione forms.

  • The paper identifies disease-specific patterns across the six measured metabolites (NAD+, NADH, NADP+, NADPH, GSH, GSSG).
  • These patterns are referred to as 'redox fingerprints' that differ between disease types.
  • The diseases examined include multiple degenerative conditions and cancers.
  • The authors state that 'redox profiling' has 'potential as an indicator of probable pathology and as a measure of treatment response.'

Low NAD+/NADH ratio occurs in specific diseases that are treated with high-dose B3-vitamin NAD+-boosters.

  • The NAD+/NADH ratio is described as increasing during fasting and being associated with health outcomes in model systems.
  • A low ratio is specifically linked to certain diseases in the literature context provided.
  • These disease states motivate the clinical use of NAD+-booster treatments.
  • The study's workflow allows direct measurement of this ratio from a single whole-blood sample.

Prior to this study, healthy human reference values as well as NAD+-booster-treated and disease-related levels of NAD(P)(H) and glutathione had not been established in humans.

  • The authors state that 'neither healthy human values nor NAD+ booster-treated or disease-related levels of NAD(P)(H) or glutathione have been established in humans.'
  • This gap in knowledge motivated the development of the standardized measurement workflow.
  • The study provides the first systematic reference dataset for these metabolites across health, disease, aging, and treatment contexts in humans.

What This Means

This research suggests that it is now possible to measure six key metabolites involved in the body's energy and antioxidant systems — NAD+, NADH, NADP+, NADPH, glutathione (GSH), and oxidized glutathione (GSSG) — all from a single blood sample using a standardized laboratory method. By applying this method to healthy adults between ages 18 and 70, the researchers found that these metabolite levels are normally distributed in the population and do not significantly change with age within this range, establishing for the first time what 'healthy' blood levels of these molecules look like in humans. This is important because until now, no such reference values existed, making it difficult to interpret whether a patient's levels were abnormal. The study also found that when healthy people took high doses of nicotinic acid (a form of vitamin B3 marketed as an NAD+ booster), their blood NAD+ levels rose dramatically — by 4 to 6 times — but the response varied considerably between individuals. This research suggests that one-size-fits-all dosing of NAD+ supplements may be inadequate, and that personalized monitoring may be needed during treatment or clinical trials. Additionally, different diseases — including various cancers and other degenerative conditions — showed distinct patterns, or 'redox fingerprints,' across these six metabolites, suggesting that this type of blood test could potentially help identify disease states or track how well a treatment is working. Overall, this work lays the groundwork for using blood redox profiling as a practical clinical tool. By knowing what normal looks like and how specific diseases and treatments alter these metabolite profiles, clinicians and researchers may be better equipped to detect pathology early, monitor disease progression, and evaluate the effectiveness of therapies that target the body's redox systems.

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Citation

Euro L, Haimilahti K, Jansson S, Forsström S, Buzkova J, Suomalainen A. (2026). Dynamics of blood NAD and glutathione in health, disease, aging, and under NAD+-booster treatment.. Redox biology. https://doi.org/10.1016/j.redox.2026.104343