+ MODEL

Journal of the Formosan Medical Association xxx (xxxx) xxx

Available online at www.sciencedirect.com

ScienceDirect

journal homepage: www.jfma-online.com

Original Article

Anemia, hematinic deficiencies, and gastric

parietal cell antibody positivity in atrophic
glossitis patients with or without
hyperhomocysteinemia
Chun-Pin Chiang a,b,c,d, Yang-Che Wu e,
Julia Yu-Fong Chang b,c,d, Yi-Ping Wang b,c,d,
Yu-Hsueh Wu a,b, Andy Sun b,c,*

a
Department of Dentistry, Far Eastern Memorial Hospital, New Taipei City, Taiwan
b
Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei,
Taiwan
c
Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan
University, Taipei, Taiwan
d
Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
e
School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan

Received 23 July 2019; accepted 2 August 2019

KEYWORDS Background/Purpose: Our previous study found that 127 of 1064 atrophic glossitis (AG) patients
Atrophic glossitis; have hyperhomocysteinemia. This study assessed whether the AG patients with hyperhomocys-
Folic acid deficiency; teinemia had significantly higher frequencies of anemia, hematinic deficiencies, and serum
Hyperhomo- gastric parietal cell antibody (GPCA) positivity than AG patients without hyperhomocysteine-
cysteinemia; mia or healthy control subjects.
Pernicious anemia; Methods: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine,
Vitamin B12 and GPCA levels in 127 AG patients with hyperhomocysteinemia, 937 AG patients without hy-
deficiency perhomocysteinemia, and 532 healthy control subjects were measured and compared.
Results: We found that 127 AG patients with hyperhomocysteinemia had significantly higher
frequencies of blood Hb and serum iron, vitamin B12, and folic acid deficiencies and serum
GPCA positivity than 532 healthy control subjects (all P-values < 0.001) and significantly higher
frequencies of blood Hb and serum vitamin B12 and folic acid deficiencies and serum GPCA pos-
itivity than 937 AG patients without hyperhomocysteinemia (all P-values < 0.001). Moreover,
127 AG patients with hyperhomocysteinemia had significantly higher frequencies of macrocytic
anemia and significantly lower frequencies of normocytic anemia than 937 AG patients without
hyperhomocysteinemia (both P-values < 0.001). Pernicious anemia (22 cases) was found

* Corresponding author. Department of Dentistry, National Taiwan University Hospital, No. 1, Chang-Te Street, Taipei 10048, Taiwan. Fax:
þ2 2389 3853.
E-mail address: andysun7702@yahoo.com.tw (A. Sun).

https://doi.org/10.1016/j.jfma.2019.08.002
0929-6646/Copyright ª 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article as: Chiang C-P et al., Anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in atrophic
glossitis patients with or without hyperhomocysteinemia, Journal of the Formosan Medical Association, https://doi.org/10.1016/
j.jfma.2019.08.002
 + MODEL
2 C.-P. Chiang et al.

only in AG patients with hyperhomocysteinemia but not in AG patients without

hyperhomocysteinemia.
Conclusions: AG patients with hyperhomocysteinemia had significantly higher frequencies of
anemia, serum iron, vitamin B12, and folic acid deficiencies, and serum GPCA positivity than
healthy control subjects and significantly higher frequencies of anemia, serum vitamin B12 and
folic acid deficiencies, and serum GPCA positivity than AG patients without hyperhomocystei-
nemia.
Copyright ª 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).

Introduction hyperhomocysteinemia and the other consisting of 937 AG

Atrophic glossitis (AG) is a disease that is defined as having
partial or complete absence or flattering of filiform papillae
on the dorsal surface of the tongue.1 Our previous study
found that 127 (11.9%) of 1064 AG patients have hyper-
homocysteinemia.1 Serum homocysteine level is a
biomarker of cardiovascular diseases. Higher serum homo-
cysteine levels are associated with increased rates of cor-
onary heart disease and stroke, because previous studies
have demonstrated that high serum homocysteine level can
cause oxidative stress, damage endothelium, and enhance
thrombogenicity.2e7 Homocysteine is formed during
methionine metabolism.2 Both vitamin B12 and folic acid
act as coenzymes for the conversion of homocysteine to
methionine.3 Moreover, vitamin B6 is a coenzyme for the
conversion of homocysteine to cysteine.3 Therefore, pa-
tients with vitamin B12, folic acid, and/or vitamin B6 de-
ficiencies may have hyperhomocysteinemia.3,4
Furthermore, the serum GPCA can destroy gastric parietal
cells, resulting in lack of intrinsic factors and hypochlo-
rhydria.8 Intrinsic factor deficiency may lead to malab-
sorption of vitamin B12 from terminal ileum and finally the
vitamin B12 deficiency.8e12 In addition, decreased gastric
secretion of hydrochloric acid may cause iron malabsorp-
tion and subsequent iron deficiency.13 Thus, it is interesting
to know whether AG patients with hyperhomocysteinemia
are prone to have significantly higher frequencies of ane-
mia, serum iron, vitamin B12, and folic acid deficiencies,
and serum GPCA positivity than AG patients without
hyperhomocysteinemia or healthy control subjects.
In our oral mucosal disease clinic, patients with AG,
burning mouth syndrome, oral lichen planus, recurrent
aphthous stomatitis, oral submucous fibrosis, or oral pre-
cancerous lesions are frequently encountered and patients
with Behcet’s disease are less commonly seen.1,14e64 For
patients with one of these seven specific diseases, com-
plete blood count, serum iron, vitamin B12, folic acid, ho-
mocysteine, GPCA, thyroglobulin antibody, and thyroid
microsomal antibody levels are frequently examined to
assess whether these patients have anemia, hematinic de-
ficiencies, hyperhomocysteinemia, and serum GPCA,
thyroglobulin antibody, and thyroid microsomal antibody
positivities.1,14e64
In this study, we divided the 1064 AG patients into two
groups: one containing 127 AG patients with
patients without hyperhomocysteinemia.1 We tried to find
out whether the AG patients with hyperhomocysteinemia
had significantly higher frequencies of anemia, serum iron,
vitamin B12, and folic acid deficiencies, and serum GPCA
positivity than AG patients without hyperhomocysteinemia
or healthy control subjects.
Materials and methods
Subjects
This study consisted of 127 (41 men and 86 women, age
range 20e90 years, mean age 69.9  14.0 years) AG pa-
tients with hyperhomocysteinemia and 937 (109 men and
828 women, age range 23e90 years, mean age 61.7  12.5
years) AG patients without hyperhomocysteinemia. For two
AG patients, one age- (2 years of each patient’s age) and
sex-matched healthy control subject was selected. Thus,
532 healthy control subjects (75 men and 457 women, age
range 20e89 years, mean age 61.7  13.9 years) were
selected and included in this study. These 127 AG patients
with hyperhomocysteinemia, 937 AG patients without
hyperhomocysteinemia, and 532 healthy control subjects
were retrieved from our previous study.1 All the AG patients
and healthy control subjects were seen consecutively,
diagnosed, and treated in the Department of Dentistry,
National Taiwan University Hospital (NTUH) from July 2007
to July 2017. Patients were diagnosed as having AG when
they had partial or complete absence or flattering of fili-
form papillae on the dorsal surface of the tongue.1,14e17
The detailed including and excluding criteria for our AG
patients and healthy control subjects have been described
previously.1,14e17 In addition, none of the AG patients had
taken any prescription medication for AG at least 3 months
before entering the study.
The blood samples were drawn from 127 AG patients
with hyperhomocysteinemia, 937 AG patients without
hyperhomocysteinemia, and 532 healthy control subjects
for the measurement of complete blood count, serum iron,
vitamin B12, folic acid, and homocysteine concentrations,
and the serum GPCA positivity. All AG patients and healthy
control subjects signed the informed consents before
entering the study. This study was reviewed and approved
by the Institutional Review Board at the NTUH.

Please cite this article as: Chiang C-P et al., Anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in atrophic
glossitis patients with or without hyperhomocysteinemia, Journal of the Formosan Medical Association, https://doi.org/10.1016/
j.jfma.2019.08.002
 + MODEL
Atrophic glossitis patients with hyperhomocysteinemia 3

Determination of blood hemoglobin, iron, vitamin

Table 1 Comparisons of mean corpuscular volume (MCV) and mean blood concentrations of hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine between any

Homocysteine

Comparisons of means of parameters between 127 AG patients with hyperhomocysteinemia or 937 AG patients without hyperhomocysteinemia and 532 healthy control subjects by
two of three groups of 127 atrophic glossitis (AG) patients with hyperhomocysteinemia, 937 AG patients without hyperhomocysteinemia, and 532 healthy control subjects.
B12, folic acid, and homocysteine concentrations

23.7  23.3

7.5  1.9

8.1  2.0
<0.001
<0.001

<0.001
The complete blood count and serum iron, vitamin B12,

(mM)
folic acid, and homocysteine concentrations were deter-
mined by the routine tests performed in the Department of

Comparisons of means of parameters between 127 AG patients with hyperhomocysteinemia and 937 AG patients without hyperhomocysteinemia by Student’s t-test.
Laboratory Medicine, NTUH.1,15e17

12.9  7.6

15.4  6.4

14.9  5.8
Folic acid
(ng/mL)
Determination of serum gastric parietal cell

<0.001
0.001

0.137
antibody level

The serum GPCA level was detected by the indirect

immunofluorescence technique with rat stomach as a sub-

410.9  308.1

723.9  251.3

697.9  226.1
strate as described previously.14e17 Sera were scored as

Vitamin B12
positive when they produced fluorescence at a dilution of

(pg/mL)

<0.001
<0.001
10-fold or more.

0.048
Statistical analysis

79.2  29.6

88.7  31.2

98.5  27.6
Comparisons of the mean corpuscular volume (MCV) and

(n Z 828)

(n Z 457)
(n Z 86)
mean blood concentrations of hemoglobin (Hb), iron,

Women

<0.001

<0.001
vitamin B12, folic acid, and homocysteine between 127 AG

0.007
Iron (mg/dL)
patients with hyperhomocysteinemia or 937 AG patients
without hyperhomocysteinemia and 532 healthy control
subjects as well as between 127 AG patients with hyper-

104.3  28.0
homocysteinemia and 937 AG patients without hyper-

86.3  33.4

94.0  32.9
(n Z 109)
homocysteinemia were performed by Student’s t-test. The

(n Z 41)

(n Z 75)
differences in frequencies of microcytosis (defined as

0.003
0.205

0.028
< 80 fL),13,57
Men

MCV macrocytosis (defined as

MCV S 100 fL), 54e56
blood Hb, iron, vitamin B12, and folic
acid deficiencies, and serum GPCA positivity between 127
AG patients with hyperhomocysteinemia or 937 AG patients
11.9  1.6

13.0  1.3

13.6  0.7
without hyperhomocysteinemia and 532 healthy control
(n Z 828)

(n Z 457)
(n Z 86)

subjects as well as between 127 AG patients with hyper-

Women

<0.001
<0.001

<0.001
homocysteinemia and 937 AG patients without hyper-
Hb (g/dL)

homocysteinemia were compared by chi-square test.

Comparisons of frequencies of macrocytic, normocytic or
microcytic anemia between 127 AG patients with hyper-
homocysteinemia and 937 AG patients without hyper-
12.7  1.5

14.3  1.8

15.1  0.8
(n Z 109)
(n Z 41)

(n Z 75)
homocysteinemia were performed by chi-square test, too.
<0.001
<0.001

<0.001

In addition, comparisons of frequencies of patients with

Men

low, moderate, or high serum levels of iron, vitamin B12,

and folic acid between 127 AG patients with hyper-
homocysteinemia and 937 AG patients without hyper-
94.6  10.6

homocysteinemia were also performed by chi-square test.

89.4  7.3

90.4  3.5

The result was considered to be significant if the P-value

MCV (fL)

<0.001
<0.001

was less than 0.05.

0.003

Results
hyperhomocysteinemia

hyperhomocysteinemia

Comparisons of MCV and mean blood concentrations of Hb,

Healthy control subjects

iron, vitamin B12, folic acid, and homocysteine between

any two of three groups of 127 AG patients with hyper-
AG patients without

homocysteinemia, 937 AG patients without hyper-

AG patients with

Student’s t-test.

homocysteinemia, and 532 healthy control subjects are

(n Z 127)

(n Z 937)

(n Z 532)

shown in Table 1. Because men usually had higher blood

levels of Hb and iron than women, these two mean levels
P-value
P-value

P-value
Group

were calculated separately for men and women. We found

significantly lower mean blood Hb (for men and women),
b
a
b
a

iron (for men and women), vitamin B12, and folic acid

Please cite this article as: Chiang C-P et al., Anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in atrophic
glossitis patients with or without hyperhomocysteinemia, Journal of the Formosan Medical Association, https://doi.org/10.1016/
j.jfma.2019.08.002
 + MODEL
4 C.-P. Chiang et al.

levels as well as significantly higher MCV and mean serum

Comparisons of frequencies of parameters between 127 AG patients with hyperhomocysteinemia or 937 AG patients without hyperhomocysteinemia and 532 healthy control subjects
Table 2 Comparisons of frequencies of microcytosis (mean corpuscular volume or MCV < 80 fL), macrocytosis (MCV S 100 fL), blood hemoglobin (Hb), iron, vitamin B12, and

GPCA positivity
folic acid deficiencies, and gastric parietal cell antibody (GPCA) positivity between any two of three groups of 127 atrophic glossitis (AG) patients with hyperhomocysteinemia,
homocysteine level in 127 AG patients with hyper-
homocysteinemia than in 532 healthy control subjects (all

234 (25.0)
50 (39.4)
P-values < 0.001, Table 1). Moreover, we also found

12 (2.3)
<0.001
<0.001

<0.001
significantly lower mean blood Hb (for men and women),

Comparisons of frequencies of parameters between 127 AG patients with hyperhomocysteinemia and 937 AG patients without hyperhomocysteinemia by chi-square test.
iron (for women only), vitamin B12, and folic acid levels as
well as significantly higher MCV and mean serum homocys-
teine level in 127 AG patients with hyperhomocysteinemia

Folic acid deficiency

than in 937 AG patients without hyperhomocysteinemia (all
P-values < 0.01, Table 1). Furthermore, 937 AG patients
without hyperhomocysteinemia also had significantly lower

(<4 ng/mL)
MCV, mean blood Hb (for men and women), iron (for men

16 (12.6)

<0.001
<0.001
8 (0.9)

0 (0.0)
and women), and homocysteine levels as well as signifi-

0.077
cantly higher serum vitamin B12 level than healthy control
subjects (all P-values < 0.05, Table 1).
According to the World Health Organization (WHO)

(<200 pg/mL)
criteria, microcytosis of erythrocyte was defined as having

Vitamin B12
deficiency
MCV < 80 fL,13,57 macrocytosis of erythrocyte was defined

50 (39.4)

<0.001
<0.001
as having MCV S 100 fL,54e56 and men with Hb < 13 g/dL

6 (0.6)

0 (0.0)
0.154
and women with Hb < 12 g/dL were defined as having Hb
deficiency or anemia.65 Furthermore, patients with the

Patient number (%)

serum iron level < 60 mg/dL,66 the serum vitamin B12

Iron deficiency
level < 200 pg/mL,67 or the serum folic acid level < 4 ng/

(<60 mg/dL)
mL68 were defined as having iron, vitamin B12 or folic acid

151 (16.1)
29 (22.8)
deficiency, respectively. In addition, patients with the

<0.001

<0.001
0 (0.0)
0.077
blood homocysteine level >12.1 mM (which was the mean
serum homocysteine level of healthy control subjects plus
two standard deviations) were defined as having hyper-

women < 12 g/dL)

homocysteinemia. By the above-mentioned definitions,
(Men < 13 g/dL,
7.1%, 27.6%, 56.7%, 22.8%, 39.4%, 12.6%, and 39.4% of 127
Hb deficiency
AG patients with hyperhomocysteinemia and 7.5%, 0.6%,

130 (13.9)
13.9%, 16.1%, 0.6%, 0.9%, and 25.0% of 937 AG patients
72 (56.7)

<0.001
<0.001

<0.001
937 AG patients without hyperhomocysteinemia, and 532 healthy control subjects.

without hyperhomocysteinemia were diagnosed as having

0 (0.0)
microcytosis, macrocytosis, blood Hb, iron, vitamin B12,
and folic acid deficiencies, and serum GPCA positivity,
respectively. We found that 127 AG patients with hyper-
(MCV S 100 fL)

homocysteinemia had significantly higher frequencies of

Macrocytosis

microcytosis, macrocytosis, blood Hb and serum iron,

35 (27.6)

vitamin B12, and folic acid deficiencies, and serum GPCA

<0.001
<0.001
6 (0.6)

0 (0.0)
positivity than 532 healthy control subjects (all P-
0.154

values < 0.001) and significantly higher frequencies of

macrocytosis, blood Hb, serum vitamin B12 and folic acid
deficiencies, and serum GPCA positivity than 937 AG pa-
(MCV < 80 fL)
Microcytosis

tients without hyperhomocysteinemia (all P-

values < 0.001). Moreover, 937 AG patients without
70 (7.5)
<0.001

<0.001
9 (7.1)

0 (0.0)

hyperhomocysteinemia had significantly higher frequencies

0.980

of microcytosis, blood Hb and serum iron deficiencies, and

serum GPCA positivity than healthy control subjects (all P-
values < 0.001, Table 2).
hyperhomocysteinemia (n Z 127)

hyperhomocysteinemia (n Z 937)

Healthy control subjects (n Z 532)

We also found that 72 (56.7%) of 127 AG patients with

hyperhomocysteinemia and 130 (13.9%) of 937 AG patients
without hyperhomocysteinemia had anemia (defined as
having an Hb concentration < 13 g/dL for men and <12 g/
dL for women).65 Of the 72 anemic AG patients with
hyperhomocysteinemia, 22 had pernicious anemia (PA,
AG patients without

defined as having anemia, an MCV S 100 fL, a serum

by chi-square test.
AG patients with

vitamin B12 level < 200 pg/mL, and the presence of serum
GPCA positivity),54e56 7 had macrocytic anemia (defined as
having anemia and an MCV S 100 fL) rather than PA,54e56
P-value
P-value

P-value
Group

35 had normocytic anemia (defined as having anemia and

an MCV between 80 fL and 99.9 fL),38e40,69e72 5 had iron
b
a
b
a

deficiency anemia (IDA, defined as having anemia, an

Please cite this article as: Chiang C-P et al., Anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in atrophic
glossitis patients with or without hyperhomocysteinemia, Journal of the Formosan Medical Association, https://doi.org/10.1016/
j.jfma.2019.08.002
 + MODEL
Atrophic glossitis patients with hyperhomocysteinemia 5

MCV < 80 fL, and a serum iron level < 60 mg/dL),13,65 and
two had thalassemia trait-induced anemia (defined as
having anemia, a RBC count > 5.0 M/mL, an MCV < 74 fL,
and a Mentzer index (MCV/RBC) < 13),58 and one had
microcytic anemia (defined as having anemia and an
MCV < 80 fL)57,66 rather than IDA and thalassemia trait-
induced anemia (Table 3). Of the 130 anemic AG patients
without hyperhomocysteinemia, one had macrocytic ane-
mia rather than PA, 82 had normocytic anemia, 25 had IDA,
19 had thalassemia trait-induced anemia, and three had
microcytic anemia rather than IDA and thalassemia trait-
induced anemia (Table 3). These findings indicate that by
strict WHO criteria the normocytic anemia and PA are the
two most common types of anemia in our 127 AG patients
with hyperhomocysteinemia. Moreover, the normocytic
anemia, IDA, and thalassemia trait-induced anemia are the
three most common types of anemia in our 937 AG patients
without hyperhomocysteinemia.
Comparisons of frequencies of macrocytic, normocytic
or microcytic anemia between 127 AG patients with
hyperhomocysteinemia and 937 AG patients without
hyperhomocysteinemia are shown in Table 4. We found that
127 AG patients with hyperhomocysteinemia had a signifi-
cantly higher frequency of macrocytic anemia and a
significantly lower frequency of normocytic anemia than
937 AG patients without hyperhomocysteinemia (both P-
values < 0.001, Table 4).
Distribution of patients with low, moderate, or high
serum levels of iron, vitamin B12, and folic acid in 127 AG
patients with hyperhomocysteinemia and in 937 AG patients
without hyperhomocysteinemia is shown in Table 5. We
found that 127 AG patients with hyperhomocysteinemia had
significantly higher frequencies of serum vitamin B12 and
folic acid deficiencies than 937 AG patients without hyper-
homocysteinemia (both P-values < 0.001). However, 937 AG
patients without hyperhomocysteinemia had significantly
higher frequencies of patients with serum vitamin B12 level
between 200 pg/mL and 800 pg/mL or 800 pg/mL and of
patients with serum folic acid level 15 ng/mL than 127 AG
patients with hyperhomocysteinemia.
Discussion
This study found that 127 AG patients with hyper-
homocysteinemia had significantly higher frequencies of
microcytosis (7.1%), macrocytosis (27.6%), anemia (56.7%),
serum iron (22.8%), vitamin B12 (39.4%), and folic acid
(12.6%) deficiencies, and serum GPCA positivity (39.4%)
than 532 healthy control subjects (all P-values < 0.001).
Our previous study demonstrated that 284 GPCA-positive
AG patients have significantly higher frequencies of
microcytosis (6.3%), macrocytosis (8.1%), anemia (22.2%),
serum iron (19.7%), vitamin B12 (10.9%), and folic acid
(1.4%) deficiencies, and hyperhomocysteinemia (18.0%)
than 532 healthy control subjects (all P-values < 0.001
except that for folic acid deficiency, P < 0.05).15 These
findings indicate that when hyperhomocysteinemia and
serum GPCA positivity are used as biomarkers to predict the
frequencies of macrocytosis, anemia, and serum vitamin
B12 deficiency in AG patients, hyperhomocysteinemia
seems to be a better predictor than serum GPCA positiv-
ity.15 Moreover, when a physician wants to check the serum
vitamin B12 and folic acid levels for a patient who is sus-
pected to have serum vitamin B12 and/or folic acid de-
ficiencies, concomitant examination of the serum
homocysteine and GPCA levels are necessary. Furthermore,
when the patients are discovered to have hyper-
homocysteinemia, they are suggested to give vitamin B12
and/or folic acid supplement treatments even if they have

Table 3 Anemia types and hematinic deficiencies of 72 anemic atrophic glossitis (AG) patients with hyperhomocysteinemia
and of 130 anemic AG patients without hyperhomocysteinemia.
Anemia type Patient number (%)
Patient number (%) Mean corpuscular Iron deficiency Vitamin B12 deficiency Folic acid
volume (fL) (<60 mg/dL) (<200 pg/mL) deficiency
(<4 ng/mL)
AG patients with hyperhomocysteinemia (n Z 127)
Pernicious anemia 22 (30.6) S100 9 (40.9) 22 (100.0) 1 (4.5)
Other macrocytic anemia 7 (9.7) S100 0 (0.0) 6 (85.7) 0 (0.0)
Normocytic anemia 35 (48.6) 80e99.9 7 (20.0) 3 (8.6) 6 (17.1)
Iron deficiency anemia 5 (6.9) <80 5 (100.0) 3 (60.0) 0 (0.0)
Thalassemia trait-induced anemia 2 (2.8) <74 0 (0.0) 0 (0.0) 1 (50.0)
Other microcytic anemia 1 (1.4) <80 0 (0.0) 1 (100.0) 0 (0.0)
Total 72 (100.0) 21 (29.2) 35 (48.6) 8 (11.1)
AG patients without hyperhomocysteinemia (n Z 937)
Pernicious anemia 0 (0.0) S100 0 (0.0) 0 (0.0) 0 (0.0)
Other macrocytic anemia 1 (0.8) S100 0 (0.0) 0 (0.0) 0 (0.0)
Normocytic anemia 82 (63.1) 80e99.9 33 (40.2) 1 (1.2) 0 (0.0)
Iron deficiency anemia 25 (19.2) <80 25 (100.0) 0 (0.0) 1 (4.0)
Thalassemia trait-induced anemia 19 (14.6) <74 4 (21.1) 0 (0.0) 0 (0.0)
Other microcytic anemia 3 (2.3) <80 0 (0.0) 0 (0.0) 0 (0.0)
Total 130 (100.0) 62 (47.7) 1 (0.8) 1 (0.8)

Please cite this article as: Chiang C-P et al., Anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in atrophic
glossitis patients with or without hyperhomocysteinemia, Journal of the Formosan Medical Association, https://doi.org/10.1016/
j.jfma.2019.08.002
 + MODEL
6 C.-P. Chiang et al.

Table 4 Comparisons of frequencies of macrocytic, normocytic or microcytic anemia between 127 atrophic glossitis (AG)
patients with hyperhomocysteinemia and 937 AG patients without hyperhomocysteinemia.
a
Anemia type Patient number (%) P-value
AG patients with AG patients without
hyperhomocysteinemia (n Z 127) hyperhomocysteinemia (n Z 937)
Macrocytic anemia 29 (40.3) 1 (0.8) <0.001
Normocytic anemia 35 (48.6) 82 (63.1) <0.001
Microcytic anemia 8 (11.1) 47 (36.1) 0.690
Total 72 (100.0) 130 (100.0)
a
Comparison of frequencies of macrocytic, normocytic or microcytic anemia between 127 AG patients with hyperhomocysteinemia
and 937 AG patients without hyperhomocysteinemia by chi-square test.

a moderate serum vitamin B12 level (up to 600 pg/mL) or
folic acid level (up to 14 ng/mL). Compared to WHO defi-
nitions for vitamin B12, folic acid and iron deficiencies,66e68
our previous study used slightly higher cutoff points for
serum vitamin B12 (&450 pg/mL), folic acid (&6 ng/mL) or
iron (&70 mg/dL for men and &65 mg/dL for women) level
to start the relatively high doses of hematinic supplement
treatments for 176 AG patients regardless of having
hyperhomocysteinemia or not.21 We found that supple-
mentations with vitamin BC capsules plus corresponding
deficient hematinics (iron, vitamin B12, and folic acid) for
those AG patients with specific hematinic deficiencies or
with vitamin BC capsules only for those AG patients without
hematinic deficiencies can reduce the high serum homo-
cysteine levels to significantly lower levels in AG patients.21
In addition, complete regression of oral symptoms (such as
burning sensation of oral mucosa, dry mouth, numbness of
the tongue, and loss or dysfunction of taste) is found in 91
(51.7%) of 176 AG patients treated with the above-
mentioned regimens.21
The serum GPCA can induce destruction of gastric parietal
cells, resulting in failure of intrinsic factor production8 and
ileac malabsorption of vitamin B12 that finally leads to
significantly higher frequencies of macrocytosis, anemia
(including macrocytic, normocytic, and microcytic anemias),
and vitamin B12 deficiency in our 127 AG patients with
hyperhomocysteinemia than in our 937 AG patients without
hyperhomocysteinemia.9e12 However, the serum GPCA posi-
tivity was found in only 50 (39.4%) of our 127 AG patients with
hyperhomocysteinemia. Vitamin B12 and/or folic acid de-
ficiencies also play important roles in causing hyper-
homocysteinemia in patients. By WHO definitions, vitamin
B12/folic acid deficiency was noted in 64 (50.4%) of our 127 AG
patients with hyperhomocysteinemia. Moreover, serum GPCA
positivity and/or vitamin B12/folic acid deficiency were found
in 81 (63.8%) of our 127 AG patients with hyper-
homocysteinemia. This finding suggests that there may be
other factors causing hyperhomocysteinemia in our 46
hyperhomocysteinemic AG patients without serum GPCA
positivity and/or vitamin B12/folic acid deficiency. Chronic
consumption of alcohol or tobacco has been shown as the
possible causes resulting in increased serum levels of homo-
cysteine in patients.52,73,74 However, it needs further studies
to explore the exact etiologies of hyperhomocysteinemia in

Table 5 Distribution of patients with low, moderate, or high serum levels of iron, vitamin B12, and folic acid in 127 atrophic
glossitis (AG) patients with hyperhomocysteinemia and in 937 AG patients without hyperhomocysteinemia.
a
Group Patient number (%) P-value
AG patients with AG patients without
hyperhomocysteinemia (n Z 127) hyperhomocysteinemia (n Z 937)
Serum iron level (mg/dL)
<60 29 (22.8) 151 (16.1) 0.077
Between 60 and 100 64 (50.4) 458 (48.6) 0.821
100 34 (26.8) 328 (35.0) 0.082
Serum vitamin B12 level (pg/mL)
<200 50 (39.4) 6 (0.7) <0.001
Between 200 and 800 53 (41.7) 495 (52.8) 0.024
800 24 (18.9) 436 (46.5) <0.001
Serum folic acid level (ng/mL)
<4 16 (12.6) 8 (0.9) <0.001
Between 4 and 15 66 (52.0) 468 (49.9) 0.739
15 45 (35.4) 461 (49.2) 0.005
a
Comparisons of frequencies of patients with low, moderate, or high serum levels of iron, vitamin B12, and folic acid between 127 AG
patients with hyperhomocysteinemia and 937 AG patients without hyperhomocysteinemia by chi-square test.

Please cite this article as: Chiang C-P et al., Anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in atrophic
glossitis patients with or without hyperhomocysteinemia, Journal of the Formosan Medical Association, https://doi.org/10.1016/
j.jfma.2019.08.002
 + MODEL
Atrophic glossitis patients with hyperhomocysteinemia
our AG patients with hyperhomocysteinemia, especially for
those hyperhomocysteinemic AG patients without serum
GPCA positivity and/or vitamin B12/folic acid deficiency.
This study found serum iron deficiency in 29 (22.8%; 16
patients also had serum GPCA positivity) of 127 AG patients
with hyperhomocysteinemia and in 151 (16.1%; 40 patients
also had serum GPCA positivity) of 937 AG patients without
hyperhomocysteinemia. This finding indicates that the
serum GPCA-induced reduction of gastric hydrochloric acid
secretion only play a partial role in causing serum iron
deficiency in our 127 AG patients with hyper-
homocysteinemia and 937 AG patients without hyper-
homocysteinemia. Thus, there may be other factors (such
as chronic blood loss related to excessive menstrual flow or
gastrointestinal diseases, a reduced intake of iron during
old-age stage, a decreased absorption of iron in patients
who take antacids, H2-receptor antagonists, or proton
pump inhibitors, and others) that result in serum iron
deficiency in our AG patients.13
The folic acid deficiency was discovered in 16 (12.6%) of
127 AG patients with hyperhomocysteinemia and in only 8
(0.9%) of 937 AG patients without hyperhomocysteinemia.
Folic acid deficiency could be due to poor nutritional
intake, malabsorption, hepatobiliary dysfunction,
increased folate catabolism, and medication (e.g., meth-
otrexate, 5-fluoro-uracil, phenytoin, etc.).60 However, the
exact etiologies causing folic acid deficiency in our 127 AG
patients with hyperhomocysteinemia and in our 937 AG
patients without hyperhomocysteinemia may need further
studies.
In this study, 72 (56.7%) of 127 AG patients with hyper-
homocysteinemia and 130 (13.9%) of 937 AG patients
without hyperhomocysteinemia had anemia, suggesting
that more anemia patients are found in 127 AG patients
with hyperhomocysteinemia than in 937 AG patients
without hyperhomocysteinemia. The normocytic anemia
(48.6%), PA (30.6%), and macrocytic anemia other than PA
(9.7%) were the three most common types of anemia in our
127 AG patients with hyperhomocysteinemia. Moreover, the
normocytic anemia (63.1%), IDA (19.2%), and thalassemia
trait-induced anemia (14.6%) were the three most common
types of anemia in our 937 AG patients without hyper-
homocysteinemia. Further analyses demonstrated that
macrocytic anemia occurred more commonly in 127 AG
patients with hyperhomocysteinemia; this result could be
partially due to significantly higher frequencies of serum
vitamin B12 and folic acid deficiencies and serum GPCA
positivity in our 127 AG patients with hyper-
homocysteinemia than in our 937 AG patients without
hyperhomocysteinemia. Moreover, normocytic anemia
occurred more frequently in 937 AG patients without
hyperhomocysteinemia than in 127 AG patients with
hyperhomocysteinemia. The normocytic anemia in AG pa-
tients could be attributed to a mixture of conditions pro-
ducing microcytic and macrocytic anemias, chronic
diseases, inflammatory diseases, infections, bone marrow
hypoplasia, decreased production of erythropoietin or a
poor response to erythropoietin, hemolytic disorders, mild
but persistent blood loss from gastrointestinal tract, and
cytokine-induced suppression of erythropoiesis.69e72
We conclude that AG patients with hyper-
homocysteinemia had significantly higher frequencies of
Please cite this article as: Chiang C-P et al., Anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in atrophic
glossitis patients with or without hyperhomocysteinemia, Journal of the Formosan Medical Association, https://doi.org/10.1016/
j.jfma.2019.08.002
7
anemia, serum iron, vitamin B12, and folic acid de-
ficiencies, and serum GPCA positivity than healthy control
subjects and significantly higher frequencies of anemia,
serum vitamin B12 and folic acid deficiencies, and serum
GPCA positivity than AG patients without
hyperhomocysteinemia.
Conflicts of interest
The authors have no conflicts of interest relevant to this
article.
Acknowledgements
This study was supported by the grants (No. 102-2314-B-
002-125-MY3 and No. 105-2314-B-002-075-MY2) of Ministry
of Science and Technology, Republic of China.
References
1. Chiang CP, Chang JYF, Wang YP, Wu YC, Wu YH, Sun A. Signif-
icantly higher frequencies of anemia, hematinic deficiencies,
hyperhomocysteinemia, and serum gastric parietal cell anti-
body positivity in atrophic glossitis patients. J Formos Med
Assoc 2018;117:1065e71.
2. Spence JD. Homocysteine-lowering therapy: a role in stroke
prevention? Lancet Neurol 2007;6:830e8.
3. Chanarin I, Deacon R, Lumb M, Perry J. Cobalamin-folate in-
terrelations. Blood Rev 1989;3:211e5.
4. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, et al.
Homocysteine lowering with folic acid and B vitamins in
vascular disease. N Engl J Med 2006;354:1567e77.
5. Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N
Engl J Med 1998;338:1042e50.
6. Harker LA, Harlan JM, Ross R. Effect of sulfinpyrazone on ho-
mocysteine induced endothelial injury and arteriosclerosis in
baboons. Circ Res 1983;53:731e9.
7. Harker LA, Slichter SJ, Scott CR, Ross R. Homocysteinemia:
vascular injury and arterial thrombosis. N Engl J Med 1974;291:
537e43.
8. Taylor KB, Roitt IM, Doniach D, Coushman KG, Shapland C.
Autoimmune phenomena in pernicious anemia: gastric anti-
bodies. BMJ 1962;2:1347e52.
9. Snow CF. Laboratory diagnosis of vitamin B12 and folate defi-
ciency. A guide for the primary care physician. Arch Intern Med
1999;159:1289e98.
10. Lahner E, Annibale B. Pernicious anemia: new insights from a
gastroenterological point of view. World J Gastroenterol 2009;
15:5121e8.
11. Oh RC, Brown DL. Vitamin B12 deficiency. Am Fam Physician
2003;67:979e86.
12. Aslinia F, Mazza JJ, Yale SH. Megaloblastic anemia and other
causes of macrocytosis. Clin Med Res 2006;4:236e41.
13. Wu YC, Wang YP, Chang JYF, Cheng SJ, Chen HM, Sun A. Oral
manifestations and blood profile in patients with iron defi-
ciency anemia. J Formos Med Assoc 2014;113:83e7.
14. Chiang CP, Chang JYF, Wang YP, Wu YH, Wu YC, Sun A. Gastric
parietal cell and thyroid autoantibodies in patients with atro-
phic glossitis. J Formos Med Assoc 2019;118:973e8.
15. Chiang CP, Chang JYF, Wang YP, Wu YH, Wu YC, Sun A. Anemia,
hematinic deficiencies, and hyperhomocysteinemia in gastric
parietal cell antibody-positive and -negative atrophic glossitis
patients. J Formos Med Assoc 2019;118:565e71.
 + MODEL
8 C.-P. Chiang et al.
16. Chiang CP, Chang JYF, Wang YP, Wu YH, Wu YC, Sun A. He-
matinic deficiencies and hyperhomocysteinemia in gastric pa-
rietal cell antibody-positive or gastric and thyroid
autoantibodies-negative atrophic glossitis patients. J Formos
Med Assoc 2019;118:1114e21.
17. Kuo YS, Wu YH, Chang JYF, Wang YP, Wu YC, Sun A. Blood
profile of atrophic glossitis patients with thyroglobulin anti-
body/thyroid microsomal antibody positivity but without
gastric parietal cell antibody positivity. J Formos Med Assoc
2019;118:1218e24.
18. Chiang CP, Chang JYF, Wang YP, Wu YC, Wu YH, Sun A. Anemia,
hematinic deficiencies, hyperhomocysteinemia, and serum
gastric parietal cell antibody positivity in atrophic glossitis
patients with or without microcytosis. J Formos Med Assoc
2019 [in press].
19. Chiang CP, Wu YH, Chang JYF, Wang YP, Wu YC, Sun A. Does
serum gastric parietal cell antibody titer have influence on
anemia and vitamin B12 deficiency in atrophic glossitis pa-
tients? J Formos Med Assoc 2019 [in press].
20. Chiang CP, Chang JYF, Wang YP, Wu YH, Wu YC, Sun A. Atrophic
glossitis: etiology, serum autoantibodies, anemia, hematinic
deficiencies, hyperhomocysteinemia, and management. J
Formos Med Assoc 2019 [in press].
21. Sun A, Wang YP, Lin HP, Chen HM, Cheng SJ, Chiang CP. Sig-
nificant reduction of homocysteine level with multiple B vita-
mins in atrophic glossitis patients. Oral Dis 2013;19:519e24.
22. Lin HP, Wang YP, Chen HM, Kuo YS, Lang MJ, Sun A. Significant
association of hematinic deficiencies and high blood homo-
cysteine levels with burning mouth syndrome. J Formos Med
Assoc 2013;112:319e25.
23. Sun A, Lin HP, Wang YP, Chen HM, Cheng SJ, Chiang CP. Sig-
nificant reduction of serum homocysteine level and oral
symptoms after different vitamin supplement treatments in
patients with burning mouth syndrome. J Oral Pathol Med
2013;42:474e9.
24. Chen HM, Wang YP, Chang JYF, Wu YC, Cheng SJ, Sun A. Sig-
nificant association of deficiencies of hemoglobin, iron, folic
acid, and vitamin B12 and high homocysteine level with oral
lichen planus. J Formos Med Assoc 2015;114:124e9.
25. Chang JYF, Chiang CP, Hsiao CK, Sun A. Significantly higher
frequencies of presence of serum autoantibodies in Chinese
patients with oral lichen planus. J Oral Pathol Med 2009;38:
48e54.
26. Chang JYF, Chen IC, Wang YP, Wu YH, Chen HM, Sun A. Anemia
and hematinic deficiencies in gastric parietal cell antibody-
positive and antibody-negative erosive oral lichen planus pa-
tients with thyroid antibody positivity. J Formos Med Assoc
2016;115:1004e11.
27. Chang JYF, Wang YP, Wu YH, Su YX, Tu YK, Sun A. Hematinic
deficiencies and anemia statuses in anti-gastric parietal cell
antibody-positive or all autoantibodies-negative erosive oral
lichen planus patients. J Formos Med Assoc 2018;117:227e34.
28. Chang JYF, Wang YP, Wu YC, Wu YH, Tseng CH, Sun A. Hema-
tinic deficiencies and anemia statuses in antigastric parietal
cell antibody-positive erosive oral lichen planus patients with
desquamative gingivitis. J Formos Med Assoc 2016;115:860e6.
29. Chang JYF, Chiang CP, Wang YP, Wu YC, Chen HM, Sun A.
Antigastric parietal cell and antithyroid autoantibodies in pa-
tients with desquamative gingivitis. J Oral Pathol Med 2017;
46:307e12.
30. Kuo RC, Lin HP, Sun A, Wang YP. Prompt healing of erosive oral
lichen planus lesion after combined corticosteroid treatment
with locally injected triamcinolone acetonide plus oral pred-
nisolone. J Formos Med Assoc 2012;112:216e20.
31. Sun A, Chang JYF, Chiang CP. Examination of circulating serum
autoantibodies and hematinics is important for treatment of
oral lichen planus. J Formos Med Assoc 2017;116:569e70.
Please cite this article as: Chiang C-P et al., Anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in atrophic
glossitis patients with or without hyperhomocysteinemia, Journal of the Formosan Medical Association, https://doi.org/10.1016/
j.jfma.2019.08.002
32. Lin HP, Wang YP, Chia JS, Sun A. Modulation of serum anti-
thyroglobulin and anti-thyroid microsomal autoantibody
levels by levamisole in patients with oral lichen planus. J
Formos Med Assoc 2011;110:169e74.
33. Lin HP, Wang YP, Chia JS, Sun A. Modulation of serum antinu-
clear antibody levels by levamisole treatment in patients with
oral lichen planus. J Formos Med Assoc 2011;110:316e21.
34. Wu KM, Wang YP, Lin HP, Chen HM, Chia JS, Sun A. Modulation
of serum smooth muscle antibody levels by levamisole treat-
ment in patients with oral lichen planus. J Formos Med Assoc
2013;112:352e7.
35. Chiang CP, Chang JYF, Wang YP, Wu YH, Lu SY, Sun A. Oral
lichen planus e differential diagnoses, serum autoantibodies,
hematinic deficiencies, and management. J Formos Med Assoc
2018;117:756e65.
36. Sun A, Chen HM, Cheng SJ, Wang YP, Chang JYF, Wu YC, et al.
Significant association of deficiency of hemoglobin, iron,
vitamin B12, and folic acid and high homocysteine level with
recurrent aphthous stomatitis. J Oral Pathol Med 2015;44:
300e5.
37. Wu YC, Wu YH, Wang YP, Chang JYF, Chen HM, Sun A. Anti-
gastric parietal cell and antithyroid autoantibodies in patients
with recurrent aphthous stomatitis. J Formos Med Assoc 2017;
116:4e9.
38. Wu YC, Wu YH, Wang YP, Chang JYF, Chen HM, Sun A. Hema-
tinic deficiencies and anemia statuses in recurrent aphthous
stomatitis patients with or without atrophic glossitis. J Formos
Med Assoc 2016;115:1061e8.
39. Wu YH, Chang JYF, Wang YP, Wu YC, Chen HM, Sun A. Anemia
and hematinic deficiencies in anti-gastric parietal cell
antibody-positive and enegative recurrent aphthous stomatitis
patients with anti-thyroid antibody positivity. J Formos Med
Assoc 2017;116:145e52.
40. Lin HP, Wu YH, Wang YP, Wu YC, Chang JYF, Sun A. Anemia and
hematinic deficiencies in anti-gastric parietal cell antibody-
positive or all autoantibodies-negative recurrent aphthous
stomatitis patients. J Formos Med Assoc 2017;116:99e106.
41. Chiang CP, Chang JYF, Sun A. Examination of serum hematinics
and autoantibodies is important for treatment of recurrent
aphthous stomatitis. J Formos Med Assoc 2018;117:258e60.
42. Chiang CP, Chang JYF, Wang YP, Wu YH, Wu YC, Sun A.
Recurrent aphthous stomatitis - etiology, serum autoanti-
bodies, anemia, hematinic deficiencies, and management. J
Formos Med Assoc 2019 [in press].
43. Kuo YS, Chang JYF, Wang YP, Wu YC, Wu YH, Sun A. Signifi-
cantly higher frequencies of hemoglobin, iron, vitamin B12,
and folic acid deficiencies and of hyperhomocysteinemia in
patients with Behcet’s disease. J Formos Med Assoc 2018;117:
932e8.
44. Lin HP, Wu YH, Chang JYF, Wang YP, Chen HM, Sun A. Gastric
parietal cell and thyroid autoantibodies in patients with Beh-
cet’s disease. J Formos Med Assoc 2018;117:505e11.
45. Wu YH, Chang JYF, Wang YP, Wu YC, Chen HM, Sun A. Gastric
parietal cell and thyroid autoantibodies in Behcet’s disease
patients with or without atrophic glossitis. J Formos Med Assoc
2018;117:691e6.
46. Wu YH, Chang JYF, Wang YP, Wu YC, Chen HM, Sun A. Hemo-
globin, iron, vitamin B12, and folic acid deficiencies and
hyperhomocysteinemia in Behcet’s disease patients with
atrophic glossitis. J Formos Med Assoc 2018;117:559e65.
47. Chiang CP, Wu YH, Chang JYF, Wang YP, Wu YC, Sun A. He-
matinic deficiencies and hyperhomocysteinemia in gastric pa-
rietal cell antibody-positive or gastric and thyroid
autoantibodies-negative Behcet’s disease patients. J Formos
Med Assoc 2019;118:347e53.
48. Chiang CP, Wu YH, Chang JYF, Wang YP, Chen HM, Sun A. Serum
thyroid autoantibodies are not associated with anemia,
 + MODEL
Atrophic glossitis patients with hyperhomocysteinemia
hematinic deficiencies, and hyperhomocysteinemia in patients
with Behcet’s disease. J Dent Sci 2018;13:256e62.
49. Chiang CP, Hsieh RP, Chen THH, ChangYF, Liu BY, Wang JT,
et al. High incidence of autoantibodies in Taiwanese patients
with oral submucous fibrosis. J Oral Pathol Med 2002;31:
402e9.
50. Wang YP, Wu YC, Cheng SJ, Chen HM, Sun A, Chang JYF. High
frequencies of vitamin B12 and folic acid deficiencies and
gastric parietal cell antibody positivity in oral submucous
fibrosis patients. J Formos Med Assoc 2015;114:813e9.
51. Chiang CP, Chang JYF, Wu YH, Sun A, Wang YP, Chen HM. He-
matinic deficiencies and anemia in gastric parietal cell
antibody-positive and -negative oral submucous fibrosis pa-
tients. J Dent Sci 2018;13:68e74.
52. Wu YH, Wu YC, Chu FY, Cheng SJ, Sun A, Chen HM. Significantly
higher frequencies of hematinic deficiencies and hyper-
homocysteinemia in oral precancer patients. J Formos Med
Assoc 2019 [in press].
53. Wu YH, Wu YC, Cheng SJ, Kuo YS, Sun A, Chen HM. Gastric
parietal cell and thyroid autoantibodies in oral precancer pa-
tients. J Formos Med Assoc 2019 [in press].
54. Sun A, Wang YP, Lin HP, Jia JS, Chiang CP. Do all the patients
with gastric parietal cell antibodies have pernicious anemia?
Oral Dis 2013;19:381e6.
55. Sun A, Chang JYF, Wang YP, Cheng SJ, Chen HM, Chiang CP. Do
all the patients with vitamin B12 deficiency have pernicious
anemia? J Oral Pathol Med 2016;45:23e7.
56. Chang JYF, Wang YP, Wu YC, Cheng SJ, Chen HM, Sun A. He-
matinic deficiencies and pernicious anemia in oral mucosal
disease patients with macrocytosis. J Formos Med Assoc 2015;
114:736e41.
57. Lin HP, Wu YH, Wang YP, Wu YC, Chang JYF, Sun A. Anemia and
hematinic deficiencies in gastric parietal cell antibody-positive
and enegative oral mucosal disease patients with micro-
cytosis. J Formos Med Assoc 2017;116:613e9.
58. Wang YP, Chang JYF, Wu YC, Cheng SJ, Chen HM, Sun A. Oral
manifestations and blood profile in patients with thalassemia
trait. J Formos Med Assoc 2013;112:761e5.
59. Sun A, Chang JYF, Wang YP, Cheng SJ, Chen HM, Chiang CP.
Effective vitamin B12 treatment can reduce serum anti-gastric
parietal cell antibody titer in patients with oral mucosal dis-
ease. J Formos Med Assoc 2016;115:837e44.
60. Chang JYF, Wang YP, Wu YC, Cheng SJ, Chen HM, Sun A. He-
matinic deficiencies and anemia statuses in oral mucosal
Please cite this article as: Chiang C-P et al., Anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in atrophic
glossitis patients with or without hyperhomocysteinemia, Journal of the Formosan Medical Association, https://doi.org/10.1016/
j.jfma.2019.08.002
9
disease patients with folic acid deficiency. J Formos Med Assoc
2015;114:806e12.
61. Chang JYF, Wang YP, Wu YC, Cheng SJ, Chen HM, Sun A. Blood
profile of oral mucosal disease patients with both vitamin B12
and iron deficiencies. J Formos Med Assoc 2015;114:532e8.
62. Sun A, Chang JYF, Chiang CP. Blood examination is necessary
for oral mucosal disease patients. J Formos Med Assoc 2016;
115:1e2.
63. Wang YP, Lin HP, Chen HM, Kuo YS, Lang MJ, Sun A. Hemo-
globin, iron, and vitamin B12 deficiencies and high blood ho-
mocysteine levels in patients with anti-thyroid autoantibodies.
J Formos Med Assoc 2014;113:155e60.
64. Chiang CP, Chang JYF, Sun A. Majority of oral mucosal disease
patients with thyroid autoantibodies have euthyroid with mi-
nority of them having either hypothyroidism or hyperthyroid-
ism. J Formos Med Assoc 2019 [in press].
65. WHO/UNICEF/UNU. Iron deficiency anaemia assessment, pre-
vention, and control: a guide for programme managers.
Geneva, Switzerland: World Health Organization; 2001.
66. Shine JW. Microcytic anemia. Am Fam Physician 1997;55:
2455e62.
67. Morris MS, Jacques PF, Rosenberg IH, Selhub J. Folate and
vitamin B-12 status in relation to anemia, macrocytosis, and
cognitive impairment in older Americans in the age of folic acid
fortification. Am J Clin Nutr 2007;85:193e200.
68. de Benoist B. Conclusions of a WHO technical consultation on
folate and vitamin B12 deficiencies. Food Nutr Bull 2008;29:
S238e44. suppl.
69. Brill JR, Baumgardner DJ. Normocytic anemia. Am Fam Physi-
cian 2000;62:2255e63.
70. Koury MJ. Abnormal erythropoiesis and the pathophysiology of
chronic anemia. Blood Rev 2014;28:49e66.
71. Koury MJ, Rhodes M. How to approach chronic anemia. Hem-
atol Am Soc Hematol Educ Progr 2012;2012:183e90.
72. Means Jr RT. Pathogenesis of the anemia of chronic disease: a
cytokine-mediated anemia. Stem Cells 1995;13:32e7.
73. Bleich S, Bleich K, Kropp S, Bittermann HJ, Degner D,
Sperling W, et al. Moderate alcohol consumption in social
drinkers raises plasma homocysteine levels: a contradiction to
the ’French Paradox’? Alcohol Alcohol 2001;36:189e92.
74. Bleich S, Carl M, Bayerlein K, Reulbach U, Biermann T,
Hillemacher T, et al. Evidence of increased homocysteine
levels in alcoholism: the Franconian alcoholism research
studies (FARS). Alcohol Clin Exp Res 2005;29:334e6.