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.
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.
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).
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.

BACKGROUND: The mechanisms of age-dependent reproductive decline in men are largely overlooked. An age-dependent reduction in nicotinamide adenine dinucleotide (NAD+) levels has been reported in multiple somatic and female reproductive tissues, including oocytes and ovarian tissue. However, the relationship between NAD + levels and male reproduction has not yet been studied. In the current study, the association between sperm NAD + level and paternal age was investigated. In addition, we also investigated whether sperm NAD + levels were related to semen quality.
METHODS: In this pilot observational cohort study, semen samples from 51 male subjects who visited a university-affiliated reproductive medical center for preconception consultation (< 30 years: n = 13, 30-40 years: n = 19, > 40 years: n = 19) were recruited. Their anthropometric characteristics were recorded, and semen analysis was performed. Their sperm NAD + levels were evaluated spectrophotometrically.
RESULTS: There were significant differences among the three age groups in the major parameters of semen quality. The sperm NAD + level was, however, similar among the three groups (< 30 years: 91.61 ± 15.59 nmol/106 sperm, 30-40 years: 125.60 ± 16.28 nmol/106 sperm, > 40 years: 115.59 ± 16.55 nmol/106 sperm). Additionally, linear regression also revealed no correlation between sperm NAD + concentration and the age of the participants (r2 = 0.018, p = 0.35). Noticeably, a negative correlation was found between the sperm NAD + concentrations and the sperm quality parameters, including sperm concentration (r2 = 0.78, p < 0.0001), sperm count (r2 = 0.47, p < 0.0001), mobile sperm number (r2 = 33, p < 0.0001), and DFI (r2 = 0.35, p < 0.0001). The semen volume and mobility rate were not related to the sperm NAD + concentration.
CONCLUSIONS: Unlike the age-related decrease of NAD + levels in oocytes and ovarian tissue, the sperm NAD + concentration is not age dependent. Sperm NAD + levels are negatively correlated with sperm quality, suggesting a unique role of NAD + in spermatogenesis, which warrants further study and opens opportunities for pharmaceutical interventions for oligozoospermia.

Nicotinamide adenine dinucleotide (NAD+ ) level is the protective factor of cardiovascular diseases (CVDs). In addition, anaemia is a risk factor of adverse cardiovascular outcomes in women. However, there are limited data about the association between NAD+ and anaemia. The aim of this study was to evaluate association of NAD+ with anaemia among women. A total of 727 females from Jidong community were included in the current analysis. NAD+ levels were tested by the cycling assay and HPLC assay using whole blood samples. Anaemia was determined by haemoglobin (Hb) concentration, and the subtypes of anaemia were further defined according to mean corpuscular volume (MCV) in blood. Multivariable logistic analysis was used to analyse the association between NAD+ levels and anaemia or its subtypes. The mean age of recruited subjects was 42.7 years. The proportion of anaemia by NAD+ levels quartiles were 19.7% (35/178), 4.8% (9/189), 3.4% (6/178) and 2.7% (5/182). Haematological parameters including haemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and red blood count (RBC) increased over NAD+ quartiles. Red cell volume distribution width (RDW) decreased over NAD+ quartiles. Compared with the lowest quartile of NAD+ levels (<27.6μM), the adjusted odds ratios with 95% confidence intervals of the top quartile were 0.15 (0.06-0.41) for anaemia, 0.05 (0.01-0.36) for microcytic anaemia and 0.37 (0.10-1.36) for normocytic anaemia respectively. Higher NAD+ levels were significantly associated with lower prevalence of anaemia among women, especially microcytic anaemia and normocytic anaemia. Haematological parameters might serve as a predictor of the blood NAD+ levels.

We conducted a double-blinded phase I clinical trial to establish whether nicotinamide adenine dinucleotide (NAD) replenishment therapy, via oral intake of nicotinamide riboside (NR), is safe, augments cerebral NAD levels, and impacts cerebral metabolism in Parkinson\'s disease (PD). Thirty newly diagnosed, treatment-naive patients received 1,000 mg NR or placebo for 30 days. NR treatment was well tolerated and led to a significant, but variable, increase in cerebral NAD levels-measured by 31phosphorous magnetic resonance spectroscopy-and related metabolites in the cerebrospinal fluid. NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography, and this was associated with mild clinical improvement. NR augmented the NAD metabolome and induced transcriptional upregulation of processes related to mitochondrial, lysosomal, and proteasomal function in blood cells and/or skeletal muscle. Furthermore, NR decreased the levels of inflammatory cytokines in serum and cerebrospinal fluid. Our findings nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials.

It has been suggested that mitochondrial dysfunction plays a role in the pathogenesis of asthma. To test whether mitochondrial variants influence the risk of asthma, we analyzed 16,158 mtSNPs in a sample of 372 asthmatic children and 395 healthy children using the DNA pooling technique and genome wide association analysis. Stratified analysis by sex was performed to explain the differences observed between sexes in the etiology of asthma. Different variants were detected to be significant in the sample of girls and boys with the smallest adjusted p values being 1.4 × 10(-09) (mt5295) and 3.6 × 10(-12) (mt16158), respectively. Most of the significant locations found in boys are within the CYB gene and the non-coding region. For girls, most of the significant mtSNPs lie within NADH-dehydrogenase-subunits. The variants reported here have not previously been described in connection with asthma. Although further studies in other cohorts are needed to confirm these findings our study highlights the importance of the mitochondria among the factors that contribute to the risk of asthma.