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2698
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J Cell Mol Med. 2022;26:2698–2705.wileyonlinelibrary.com/journal/jcmm
Received: 30 November 2021
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Revised: 12 February 2022
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Accepted: 3 March 20 22
DOI : 10.1111/j cmm .1728 1
ORIGINAL ARTICLE
Association between NAD+ levels and anaemia among women
in community- based study
Fan Yang1 | Xuguang Zhang2 | Feifei Hu3 | Ye Yu4 | Lei Luo1 | Xuan Deng3 |
Yuzheng Zhao5 | Bo Pan6 | Jinping Zheng7 | Yugang Qiu8 | Jun Guo1 | Feng Xiao1 |
Xiaomei Xie9 | Zhenyu Ju1 | Yong Zhou3
1Institute of Aging and Regenerat ive Medi cine, The Firs t Affiliated Ho spital of Jinan University, Jinan Un iversi ty, Guangzhou, China
2Science a nd Technology Centre, By- Health C o. Ltd., Guangzhou, China
3Clinical Resea rch Institute, Shanghai General Hospital, Shanghai Jiao Tong Universit y School of Medicine, Shanghai, China
4Adminis trati ve Offi ce, Total Qualit y Management Office, Total Quality Mana gement Ins titute, Shanghai Gener al Hospit al, Shan ghai Jiao Tong University
School of Medicine, Shan ghai, China
5State Key Laboratory of Bioreac tor Engineering, Shanghai Collabor ative Innovatio n Center for Biomanufac turin g Technolog y, Optogenetics & Syntheti c
Biolog y Interd isciplinary Research Center, Research Unit of Chinese Aca demy of Medical Sciences, East C hina Universit y of Science and Technology, Sha nghai,
China
6Depar tment of Auricular Reconstruction , Plastic Surgery Hospital, Peking Union Med ical Co llege and Chinese Academy of Medical Science, Beijing, China
7Depar tment of Public Health and Preventive Medicine, Changzh i Medic al College, Chan gzhi, C hina
8School of Rehabilitatio n Medicine, Weifa ng Medical Universit y, Weifang, C hina
9Tangshan Gem Flower Hospital, Tangshan, China
This is an op en access arti cle under the ter ms of the Creative Commons Attribution L icense, which pe rmits use, dis tribu tion and reprod uction in any med ium,
provide d the original wor k is properly cited.
© 2022 The Author s. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and M olecular Medi cine and J ohn Wil ey & Sons Ltd .
Fan Yang, Xugu ang Zhang, Feif ei Hu, and Ye Yu contribu ted equa lly to this paper.
Correspondence
Yong Zhou, Clinical Researc h Institute,
Shanghai General Hospital, Shanghai
Jiao Tong University School of Medicine,
Shanghai, 200080, China.
Email: yongzhou78214@163.com
Zhenyu Ju, Key Laborator y of
Regener ative Me dicine of M inistry of
Education, Guangzhou Regenerative
Medicine and Health Guangdong
Labor atory, Institute of Aging and
Regener ative Me dicine, Jinan University,
Guangzhou 510632, China.
Email: zh enyuju@16 3.co m
Funding information
Nutrit ional Science Research Foundation
of BY- HEALTH Co. Ltd; National Key R&D
Program of China, Grant /Award Number:
2018YFC2000705 and 2021YFC2500500;
Nationa l Natural Scien ce Foundation of
China, G rant/Award Numbe r: 81973112,
92049302 and 92049304
Abstract
Nicotinamide adenine dinucleotide (NAD+) level is the protective factor of cardiovas-
cular 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) concen-
tration, and the subtypes of anaemia were further defined according to mean corpus-
cular 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 re-
cruited 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 cor-
puscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC)
and red blood count (RBC) increased over NAD+ quartiles. Red cell volume distribu-
tion width (RDW) decreased over NAD+ quartiles. Compared with the lowest quartile
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YANG et Al.
1 | INTRODUCTION
Nicotinamide adenine dinucleotide (NAD+) is a pivotal metabolite
with a wide range of roles in cell survival, mitochondrial homeosta-
sis, cellular bioenergetics, adaptive stress responses and genomic
stability.1 NAD+ is involved in over 500 enzymatic reactions in reg-
ulating almost all major biological processes.2 Meanwhile, NAD+ is
also a co- substrate of regulatory enzymes, including sirtuins (SIRTs),
poly (ADP- ribose) polymerases (PARPs) and cyclic ADPR (cADPR)
synthetases.3 The association of NAD
+ levels with cardiovascular
diseases (CVDs) including endothelial, atherosclerosis and heart
failure has been reported by a few studies.4 – 7 Loss of NAD+ con-
tents are implicated in the pathogenesis of multiple types of CVDs,
and boosting NAD+ levels seems to be a strongly protective role of
CVDs.8 Moreover, NAD precursors have been suggested to delay
the process of vascular aging and increase the span of cardiovascular
health.9
Anaemia is a worldwide health problem in the world,10– 1 3 particu-
larly so in developing countries with children and women as the most
affected population groups.14 Approximately 1.9 billion individuals
worldwide suffer from anaemia, which is nearly one- quarter of the
global population in 2013.15 The World Health Organization (WHO)
estimated that 32.4 million pregnant women and 496.3 million non-
pregnant women were anaemic across the world in 2011.16 In ad-
dition, severe anaemia in pregnant and postnatal women strongly
and independently contributes to maternal death.17 Managing
anaemia is one of the global health goals.13 In China, whose pop-
ulation accounts for more than 18% of the world, the prevalence
of anaemia is about 15.0% according to the fifth Chinese National
Nutrition and Health Sur vey (CNNHS 2010– 2012) and the anaemia
prevalence for Chinese rural reproductive age women was 24.8%
in 2012.18, 19Anaemia was defined by WHO as a lower haemoglobin
(Hb) content than normal in whole blood.20 In addition, lower Hb is
significantly and independently associated with adverse cardiovas-
cular outcomes in women.21 Anaemia is significantly correlated with
severe complications of CVDs including stroke, arrhythmias and
thromboembolics in the general population. It is also an indepen-
dent predictor of cardiovascular mortalities.2 2– 24 NAD+ levels and
anaemia are the protective factor and risk factor of CVDs respec-
tively. However, the research on the associations between NAD+
contents in whole blood and subtypes of anaemia is still in scarcity.
We assumed that NAD+ levels would be negatively correlated with
anaemia. In our current study, we sought to understand the relation-
ship of NAD+ levels with the anaemia and explore the associations
of different types of anaemia with NAD+ levels.
2 | METHOD
2.1 | Study design and population
The population in this community- bas ed stud y was from Jido ng com-
mu nit y in Tan gsh a n Cit y, Heb e i Pro vin c e, Ch ina . Fr om 20 19 to 20 2 0, a
total of 1723 participants were originally recruited into the study. We
excluded 802 males and 191 participants with incomplete informa-
tio n. Final ly, 727 fe ma le s were included in the final analysis (Figure 1).
All participants gave written informed consent, and the study was
conducted according to the guidelines of the Helsinki Declaration.
2.2 | Data collection
In this study, basic info rmati on of subject s was obt ained fro m st an d-
ardized questionnaires, laboratory tests and clinical examinations.25
Face- to- face interviews were performed by well- trained examiners.
Information on demographic characteristics including age, income
and education level was collected by standardized questionnaires.
The average monthly income was divided into ‘≤¥3000’, or ‘>¥3000’.
Ed u cat ion leve l s wer e ca te gor ize d as ‘Mi d d le sc h o ol or be l ow’ or ‘co l -
legeor above’. Body mass index (BMI) was categorized as ‘<18.5 kg/
m2’, ‘18.5– 23.9 kg/m2’, ‘24.0– 27.9 kg/m2’ and ‘>28.0 kg/m2’. Previous
history of hyperlipidaemia, hypertension and diabetes mellitus was
recorded directly by self- reports of par ticipants.
2.3 | Measurement of NAD+ levels
Blood samples were collected from the large antecubital veins after
overnight fasting. All blood samples were stored in vacuum tubes
containing EDTA (ethylene diamine tetraacetic acid), and NAD+ lev els
of NAD+ levels (<27. 6 μM), 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 normocy tic anaemia respectively. Higher NAD+ lev-
els 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.
KEYWORDS
cardiovascular diseases, hemoglobin, Nicotinamide adenine dinucleotide
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YANG e t Al.
were determined by the cycling assay and LC- MS/MS analysis in the
laboratories.26 – 29 (see Supplementary Material 1 and Figure S1).
NAD+ levels were stratified into 4 categories: Q1 (<27.6), Q2
(27.6– 31.0), Q3 (31.0– 34.5) and Q4 (≥34.5), which were based on
the quartiles of NAD+ levels. In addition, the participant s in Q2, Q3
and Q4 were grouped into Q2- 4, whose NAD+ level was in 2th- 4th
NAD+ quartile (25th percentile- 100th percentile).
2.4 | Determination of haematology parameters
Haematology parameters including haemoglobin (Hb), mean corpus-
cular volume (MCV), mean corpuscular haemoglobin (MCH), mean
corpuscular haemoglobin concentration (MCHC), red cell distribu-
tion width (RDW) and red blood count (RBC) were measured by
autoanalyzer (Hitachi 747; Hitachi,) in the central laboratory of the
Staff Hospital of the Jidong Oilfield.
2.5 | Diagnosis of anaemia
According to World Health Organization (WHO), anaemia was de-
fined as Hb concentration lower than 120 mg/dl for women.20
According to MCV, anaemia was fur ther classified into three t ypes:
microcytic anaemia if MCV was lower than 80 fl, normocy tic anae-
mia if MCV was from 80 to 100 fl, and macrocytic anaemia if MCV
was higher than 100 fl.30
2.6 | Statistical analysis
The normality distributions of continuous variables were evaluated
by the Kolmogorov– Smirnov test. Continuous variables are ex-
pressed as the mean ± standard deviation (SD) and were compared
using one- way ANOVA or t- test, as appropriate. Categorical variables
are presented as proportions and frequencies and were compared by
chi- squared tests. Multivariable logistic regression models were used
to assess the associati on betwee n NAD+ quartiles and anaemia or its
different types. We adjusted 4 covariates which were thought to be
potential confounder of the risk factors for anaemia: age, BMI, UA
and RBC. All statistical tests were 2- sided, and p values of less than
0.05 we re consid er ed to be sign if ic ant. Sta ti st ic al ana ly se s were co n-
ducted with SAS sof tware, version 9.4 (SAS Institute Inc.,).
3 | RESULTS
3.1 | Baseline Characteristics in eligible
participants
Baseline characteristics of par ticipants according to NAD+ quartiles
are summarized in Table 1. Of 727 females finally included, the mean
age was 42.7 years and there were only 6 smokers and 5 drinkers.
BMI distributions were different among the quartiles of NAD+. The
levels of UA increased along with the levels of NAD+. Analysis of
haematological parameters in different NAD+ quartiles is also pre-
sented in Table 1. The levels of Hb, MCV, MCH, MCHC and RBC
increased along with the qua rtiles of NAD+, while the levels of RDW
dec rease d along wit h the quartiles of NAD+. Age, income, education
level, history of smoke, history of drink, salt intake, eGFR, history of
hyperlipidaemia, hypertension and diabetes were not significantly
different among the quartiles. Baseline characteristics of male and
females has been provided. (see Table S2).
3.2 | Association between NAD+
levels and anaemia
The anaemia occurred in 19.7%, 4.8%, 3.4% and 2.7% in each NAD+
quartile respectively (Figure 2). Crude and adjusted odds ratios (OR)
with 95% confiden ce inter vals (CI ) of NAD + level s fo r anaemia sta tu s
are shown in Table 2. In general, lower NAD+ levels were associated
FIGURE 1 Flow chart of this study
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YANG et Al.
with higher prevalence of anaemia. Compared with the first quartile
of NAD+, propor tion rates of anaemia in the 2th- 4th NAD+ quartile
(25th percentile- 100th percentile) was also much lower. The NAD+
levels between anaemic and non- anaemic group have been pro-
vided. (see Table S3).
3.3 | Association between quartiles of NAD+
levels and types of anaemia
Rates of types of anaemia according to quartiles of NAD+ levels
are presented in Table 3. The proportion of microcytic anaemia
and normocytic anaemia was 4.1% and 3.5%. Both of them de-
creased by NAD+ quartiles. The proportion of macrocytic anaemia
was just 0.1% (N = 2), so macroc ytic anaemia was not further ana-
lys ed in the logi st ic regression model due to few eve nt s. As shown
in Table 4, the prevalence decreased with the higher NAD+ lev-
els in microcytic anaemia and normocytic anaemia respectively;
compared with the first quartiles of NAD+, the adjusted ORs and
95% CI of the fourth NAD+ quartile were 0.05 (0.01– 0.36) for mi-
crocytic anaemia and 0.37 (0.10– 1.36) for normocytic anaemia,
and the adjusted ORs and 95% CI of the 2th~4th NAD+ quartile
(25th percentile- 100th percentile) were 0.16 (0.07– 0.36) for mi-
crocytic anaemia and 0.20 (0.07– 0.56) for normocytic anaemia.
TAB LE 1 Baseline characteristics of participants according to NAD+ quartiles
Characteristics
Overall
(n = 727)
Q1 (<27. 6)
(n = 178)
Q2 (27.6– 31.0)
(n = 189)
Q3 (31.0– 34.5)
(n = 178)
Q4 (≥34.5)
(n = 182) p value
Age (years) 42.7 ± 11. 3 41.4 ± 9.3 43.5 ± 12.4 42.9 ± 11.5 42.9 ± 11.7 0.33
Income,¥/month (n,%) 0.33
≤¥3000 52 (7.8) 8 (5.0) 13 (7.7) 17 (10.6) 14 (8.1)
>¥3000 613 (92.2) 152 (95.0) 157 (92.4) 177 (89.4) 160 (92.0)
Education level (n,%) 0.57
Middle school or below 254 (34.9) 63 (35.4) 73 (38.6) 60 (33.7) 58 (31.9)
College or above 473 (65.1) 115 (64.6) 116 (61.4) 118 (66.3) 124 (68.1)
Body mass index (k g/m2)<0.05
<18.5 99 (13.6) 23 (12.9) 25 (13.2) 29 (16.3) 22 (12.1)
18 . 5– 2 3 .9 395 (54.3) 97 (54.5) 108 (57.1) 98 (55.1) 92 (50.6)
24 . 0 – 2 7.9 178 (24.5) 53 (29.8) 4 3 (22.8) 31 (17.4) 51 (28.0)
≥28.0 55 (7.6) 5 (2.8) 13 (6.9) 20 (11.2) 17 (9.3)
Smoking (n,%) 6 (0.9) 0 (0.0) 3 (1.8) 2 (1.2) 1 (0.6) 0.43
Drinking (n,%) 5 (0.8) 2 (1.3) 0 (0.0) 2 (1.2) 1 (0.6) 0.46
Salt intake (n,%) 0.49
Low 218 (32.8) 55 (34.4) 53 (31.2) 49 (30.4) 61 (35.1)
Medium 370 (55.6) 81 (50.6) 101 (59.4) 96 (59.6) 92 (52.9)
High 77 (11.6) 24 (15.0) 16 (9.4) 16 (9.9) 21 (12.1)
Hyperlipidaemia (n,%) 256 (38.4) 56 (35.0) 59 (34.7) 60 (37.0) 81 (46 .6) 0.08
Hyper tesion (n,%) 107 (16.1) 19 (11.9) 26 (15.3) 26 (16.1) 36 (20.7) 0.18
Diabetes (n,%) 35 (5.3) 7 (4.4) 6 (3.5) 8 (4.9) 14 (8.1) 0.26
eGFR (mL/min/1.73m2)121.4 ± 24.3 121.0 ± 23.3 124.1 ± 24.4 118.7 ± 24 .4 121.9 ± 24.7 0.28
UA (μmol/L) 2 89. 9 ± 66.2 281.9 ± 61. 4 283.1 ± 61 .7 296.1 ± 68.8 298.6 ± 71.2 <0.05
Haematological parameters
Hb (g/L) 136.0 ± 1 2.1 130.1 ± 15.6 135.6 ± 11.0 138.4 ± 9.4 1 39. 8 ± 9.2 <0.0001
MCV (fL) 91.9 ± 6.4 89.9 ± 8.7 91.6 ± 6.5 93 .1 ± 4.7 93.1 ± 4.2 <0.0001
MCH (pg) 30.9 ± 2.5 30.1 ± 3.4 30.6±2.5 31.4 ± 1.7 31.4 ± 1.5 <0.0001
MCHC (g/L) 335.6 ± 8.8 334.2 ± 10.1 33 4.1 ± 8.4 337. 0 ± 7.5 33 7.2 ± 8.4 <0.0001
RDW (%) 12.2 ± 1.5 12.6 ± 2.1 12.2 ± 1.6 12.0 ± 1.1 12.0 ± 1.0 <0.01
RBC (10^12/L) 4.4 ± 0.3 4.3 ± 0.4 4.4 ± 0.3 4.4 ± 0.3 4.5 ± 0.3 <0.01
PLT (10^9/L) 22 9.7 ± 5 7. 8 235.6 ± 61. 5 235.6 ± 58.9 2 19. 5 ± 50.1 2 27. 8 ± 59.1 <0.05
WBC (10^9/L) 6.3 ± 1.5 6.3 ± 1.6 6. 3 ± 1.5 6.3 ± 1.5 6.4 ± 1.6 0.77
Abbreviations: BMI, body mass index; eGFR, estimated glomerular filtration rate; UA, uric acid; NAD+, nicotinamide adenine dinucleotide; Hb,
haemoglobin; MC V, mean corpuscular volume; MCH, mean corpuscular; MCHC, mean corpuscular haemoglobin concentration; RDW, red cell volume
distribution width; RBC, red blood cell; PLT, platelet count; WBC, white blood cell.
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YANG e t Al.
The haematological parameters in each type of anaemia have been
provided. (see Table S1).
4 | DISCUSSION
In this community- based study, individuals with the low NAD+
quartile were associated with high risk of anaemia among women.
Anaemia subtype analysis in our study showed that this associa-
tion was also evident in microcytic anaemia and normocytic anae-
mia among women. Besides, we observed a positive association
between NAD+ levels and haematological parameters including Hb,
MCV, MCH, MCHC and RBC. Our results provide evidence for the
relationship between NAD+ levels and anaemia among women.
Most of the existing studies focused on the association be-
tween NAD+ contents in RBCs and sickle cell disease (SCD).
Stu di es about th e as so ci at io n between SCD and NAD+ contents in
RBCs are controversial. Sickle RBCs had an increased NAD+ con-
tent , and this incr ease in NAD + may be th e reaso n of a dve rse met-
abolic consequences in sickle RBCs.31 However, a study reported
that the levels of NAD+ in sickle RBC s were similar to the levels in
normal RBCs.32 As reported, among patients with anaemia, 50%–
80% are iron deficiency anaemia (IDA) which is highly prevalent
among women throughout their lives.33 A study in rhesus mon-
key found that the NAD metabolites were similar between IDA
and control groups, and NAD pathway components nearly dou-
bled after the treatment of IDA.34 Another study in male chicks
found that iron deficiency reduced the utilization of tryptophan
with which de novo biosynthesis of NAD star ts.35,36 Haemolytic
anae mi a co uld be ind uc ed by m ed ic ation s along with oth er ca uses,
whose late diagnosis could be fatal.37 Nicotinamide mononucle-
otide ad enylylt ra nsfer as e 3 (Nm na t3 ) is consid er ed a NA D s yn th e-
sis enz yme involved in de novo and salvage pathways. Deficienc y
of Nmnat3 in mice can cause haemoly tic anaemia.38 In our study,
the anaemia subtypes distinguished by pathogeny like IDA and
haemolytic anaemia could not be judged and anaemia was clas-
sified into three subtypes by MCV. NAD+ levels were detected
in whole blood instead of just in RBCs. We found that low NAD+
quartile was associated with high risk of anaemia among women.
The prevalence of microcytic anaemia and normocytic anaemia
decreased with increase of NAD+ level. The specific impact of
NAD+ levels on anaemia warrants further research.
Elevated Hb was related to Sirtuin 1 (SIRT1) levels, which was the
activation of NAD- dependent deacetylase.39 A study in mice found
that replenishing NAD had a positive effect on the most primitive
blood stem cells and protected patients from haematological fail-
ure.40 These findings indicated that NAD+ might be a prote ct ive fac-
tor of anaemia and also provided a possible theoretical suppor t for
our findings. In our study, there were positive associations between
NAD+ levels and haematological parameters including Hb, MCV,
MCH, MCHC and RBC. Our result implied that, NAD+ might be a
new indicator for anaemia among women, especially in microcytic
anaemia and normocytic anaemia.
The study has several potential limitations. First, we were un-
able to determine subtype of anaemia according to the pathogeny
due to the lim ite d data. Thus, the asso ciations of anaemia su bt ypes
accord in g to th e pat ho ge ny wi th NA D+ level s ne ed to be fur ther in-
ve sti gat ed in a su bse que nt stu d y. S eco nd, th e cro ss- s e c tio nal st udy
FIGURE 2 Proportions of anaemia status according to NAD+
quartiles
Q1 Q2 Q3 Q4
0
5
10
15
20
25
19.7%
4.8%
3.4% 2.7%
Percent of participants %
TAB LE 2 Association between quartiles of NAD+ levels and anaemia among women
NAD+ Quartiles
Subjec ts with anaemia
(n,%) Unadjusted OR (95% CI) Adjusted OR (95% CI)
Q1 35 (4.8) 1 (Reference) 1 (Reference)
0.00.5 1.01.5
Q2 9 (1.2) 0.20 (0.10– 0.44) 0.25 (0.11– 0.55)
Q3 6 (0.8) 0.14 (0.06– 0.35) 0.17 (0.07– 0.43)
Q4 5 (0.7) 0.12 (0.04– 0.30) 0.15 (0.06– 0.41)
Q 2 - 4 20 (2.8) 0.15 (0.09– 0.28) 0.19 (0.10– 0.35)
Note: Covariates included age, BMI, UA and RBC .
Abbreviations: CI, confidence interval; OR, odds ratio.
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YANG et Al.
made it difficult to infer the causal effect relationship between
anaemia and NAD+ contents. Third, the participants were mainly
from an urb an ci ty in North Chin a; ther ef or e, th e fin din gs migh t not
be generalized to other ethnics and male. Finally, given the charac-
teristics of obser vational study, there might be some unmeasured
or residual confounding effects that could not be adjusted.
The study aim was to investigate the association between NAD+
level and the prevalence of anaemia subtypes distinguished by MCV
and the cor re lation of NAD + with haematological parameters among
wo men . Due to the li mit ed dat a , the as soc i ati o n bet wee n NAD + level
and specific anaemia subtypes according to the pathogeny could not
be analysis. Whether NAD+ is involved in the occurrence and de-
velopment of anaemia, has core effect or just was accompanied by
appearance, still need to be studied in future research.
In summary, the high NAD+ level in whole blood was associated
with a low prevalence of anaemia among women, especially micro-
cytic anaemia. Besides, haematological parameters including Hb,
MCV, MCH, MCHC and RBC were positively associated with NAD+
contents. Haematological parameters might serve as a predictor for
lack of NAD+ in whole blood among women.
ACKNOWLEDGMENTS
This work is supported by the National Key R&D Program of China
(2018YFC2000705 and 2021YFC2500500), National Natural
Science Foundation of China (81973112, 92049302, 9204930 4) and
Nutritional Science Research Foundation of BY- HEALTH Co. Ltd. We
thank members of the Ju group for their technical assistance for de-
tecting NAD+ levels. We thank many volunteers in this study.
CONFLICT OF INTEREST
The authors declare no competing interests.
AUTHOR CONTRIBUTIONS
Yong Zhou: Funding acquisition (equal); Project administration
(lead). Fan Yang: Data curation (lead); Formal analysis (equal);
Methodology (supporting); Writing – original draft (supporting);
Writing – review & editing (supporting). Xuguang Zhang: Data
curation (supporting); Formal analysis (supporting); Methodology
(supporting); Project administration (supporting); Writing – re-
view & editing (supporting). Feifei Hu: Data curation (equal);
Formal analysis (equal); Methodology (supporting); Project
Type of anaemia
Unadjusted OR
(95% CI) Adjusted OR (95% CI)
Microcytic anaemia
0.00.5 1.01.5
Q2 VS Q1 0. 31
(0.13– 0.76)
0.28
(0.11– 0.71)
Q3 VS Q1 0.14
(0.04– 0.48)
0.14
(0.04– 0.50)
Q4 VS Q1 0.05
(0.01– 0.34)
0.05
(0.01– 0.36)
Q2- 4 VS Q1 0.17
(0.08– 0.36)
0.16
(0.07– 0.36)
Normocytic anaemia
Q2 VS Q1 0.11
(0.02– 0.47)
0.13
(0.03– 0.67)
Q3 VS Q1 0.17
(0.05– 0.59)
0.15
(0.03– 0.69)
Q4 VS Q1 0. 22
(0.07– 0.66)
0.37
( 0 . 1 0 – 1 . 3 6 )
Q2- 4 VS Q1 0.16
(0.07– 0.38)
0.20
(0.07– 0.56)
Note: Covariates included age, BMI, UA and RBC .
Abbreviations: CI, confidence interval; OR, odds ratio.
TAB LE 4 Association between
quartiles of NAD+ levels and t ypes of
anaemia among women
NAD+ Quartiles, μM
Type of anaemia Overall
Q1
(<27. 6)
Q2
(27.6– 31.0)
Q3
(31.0– 34.5)
Q4
(≥34 .5) p value
microcytic
anaemia
29 (4.1) 18 (2.6) 7 (1.0) 3 (0.4) 1 (0.1) <0.0001
normocytic
anaemia
24 (3.5) 15 (2.2) 2 (0.3) 3 (0.4) 4 (0.6) <0.001
TAB LE 3 Rates of t ypes of anaemia
according to quartiles of NAD+ levels
among women
2704
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YANG e t Al.
adm inistr ation (su pp or ting ); Writing – or iginal draft (le ad); Writ in g
– review & editing (lead). Ye Yu: Data curation (equal); Writing
– review & editing (equal). Lei Luo: Data curation (supporting);
Formal analysis (supporting); Methodology (supporting); Project
administration (supporting). Xuan Deng: Data curation (support-
ing); Methodology (supporting); Project administration (support-
ing). Yuzheng Zhao: Data curation (supporting); Methodology
(supporting); Project administration (supporting). Bo Pan: Data
curation (supporting); Methodology (supporting); Project admin-
istration (supporting). Jin- ping Zheng: Data curation (supporting);
Methodology (supporting); Project administration (supporting).
Yugang Qiu: Data curation (supporting); Methodology (support-
ing); Project administration (supporting). Feng Xiao: Dat a curation
(supporting); Funding acquisition (supporting); Methodology (sup-
porting); Project administration (supporting). Zhenyu Ju: Data cu-
ration (equal); Formal analysis (equal); Funding acquisition (equal);
Methodology (equal); Project administration (equal); Writing
– review & editing (equal). Jun Guo: Methodology (supporting);
Validation (supporting). Xiaomei Xie: Data curation (supporting);
Investigation (supporting).
ORCID
Yong Zhou https://orcid.org/0000-0001-5221-8026
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SUPPORTING INFORMATION
Additional supporting information may be found in the online
version of the article at the publisher ’s website.
How to cite this article: Yang F, Zhang X, Hu F, et al.
Association bet ween NAD+ levels and anaemia among
women in community- based study. J Cell Mol Med.
2022;26:2698– 2705. doi:10.1111/jcmm.17281
Available via license: CC BY 4.0
Content may be subject to copyright.