Association of NAD+ levels with metabolic disease in a community-based study

Front Endocrinol (Lausanne). 2023 Apr 20:14:1164788. doi: 10.3389/fendo.2023.1164788. eCollection 2023.

Abstract

Background: Nicotinamide adenine dinucleotide (NAD+) is a coenzyme and plays a crucial role in several metabolic processes. This study explored the association of nicotinamide adenine dinucleotide (NAD+) levels with metabolic disease (MD) in adults.

Methods: In this cross-sectional study, all data were collected from the Jidong community. MD was defined as the presence of one or more of the following disease components: hypertension, dyslipidemia, diabetes, hyperuricemia, obesity, and non-alcoholic fatty liver disease (NAFLD). The MD components were categorized into three groups: those with one component, those with two components, and those with three to six components. The whole blood NAD+ level was measured using a cycling assay and LC-MS/MS analysis. The participants were divided into four groups based on their NAD+ level quartiles. Multivariable logistic regression was used to evaluate the association of the whole blood NAD+ levels with MD.

Results: Of the 1,394 eligible participants, the average age was 43.2 years, and 74.3% had MD. In the top quartile of NAD+, the prevalence of MD and each of its components (hypertension, hyperlipidemia, diabetes, hyperuricemia, obesity, and NAFLD) were 87.9% 35.2%, 62.3%, 8.7%, 36.9%, 21.0%, and 60.5%, respectively. As compared with the lowest NAD+ quartile (≤29.4 μmol/L), the adjusted odds ratios and 95% confidence interval of the highest quartile were 3.01 (1.87-4.87) for MD, 2.48 (1.44-4.29) for 1 MD component, 2.74 (1.45-5.17) for 2 MD components, and 4.30 (2.32-7.98) for 3-6 MD components. The risk of MD began to increase at NAD+ levels of 31.0 μmol/L, as revealed by the gradient associations of NAD+ levels with MD. There was no significant interaction between age, sex, drinking, smoking, and NAD+ for MD (p for interaction ≥0.10).

Conclusions: Increased NAD+ was significantly associated with MD, as well as its individual components. Our findings provide new evidence for the relationship between blood NAD+ levels and MD.

Keywords: cross-sectional study; metabolic disease; nicotinamide adenine dinucleotide; population; whole blood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromatography, Liquid
  • Cross-Sectional Studies
  • Diabetes Mellitus* / epidemiology
  • Humans
  • Hypertension* / complications
  • Hypertension* / epidemiology
  • Hyperuricemia* / complications
  • Hyperuricemia* / epidemiology
  • NAD / metabolism
  • Non-alcoholic Fatty Liver Disease* / complications
  • Obesity / complications
  • Obesity / epidemiology
  • Tandem Mass Spectrometry

Substances

  • NAD

Grants and funding

This work was supported by the National Key R&D Program of China [Grant Numbers 2021YFC2500500, 2018YFC2000704]; the National Natural Science Foundation of China [Grant Numbers 92049302, 81973112, 91749205]; the Nature Science Fund of Hunan province [Grant Number 2022JJ3051]. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.