Table 1 Detailed characteristics of included studies

Gharbi et al., 2019 [26]

Africa (Tunisia)

College

Case control

AAP criteria

Periodontal health

80 (33/47) vs. 50 (25/25)

42 ± 13.6 vs. 44.8 ± 12.6

PPD: 5.3 (2.5–7.5) vs. 1 (0.5–2)

Blood/Plasma

EBCM

5.22 ± 0.91 vs. 4.13 ± 1.11(mg/dL) ^‡

NOS:8

Banu et al., 2015 [25]

Asia (India)

Unknown

Case control

Clinically ≥ 4 teeth in each jaw; PPD ≥ 5 mm; CAL ≥ 4 mm; ≥ 80% BOP + at proximal sites; presence of ABL in ≥ 2 quadrants of the dentition; interproximal ABL ≥ 50%

Without periodontitis

40 (14/26) vs. 20 (9/11)

40–65

PPD: 5.55 ± 0.29 vs. 2.28 ± 0.13

Blood/Plasma

EBCM

5.32 ± 0.95 vs. 4.42 ± 0.68 (mg/dL)

NOS:8

Mourão et al., 2015 [55]

South America (Brazil)

Unknown

Case control

AAP criteria

PPD < 3 mm in all tooth sites and absence of CAL

20 (8/12) vs. 20 (8/12)

54.3 ± 10.02 vs. 50.2 ± 8.79

NM

Blood/Plasma

EBCM

6.45 ± 1.44 vs. 4.77 ± 0.81 (mg/dL)

NOS:7

Merle, C.L., et al., 2022 [62]

Europe (German)

University

Cross-sectional

CPITN > 2

CPITN ≤ 2

32 (17/15) vs. 53(25/28)

21.6 ± 3.9 vs. 21.4 ± 3.2

NM

Blood/Plasma

NM

4.76 ± 1.02 vs 4.22 ± 1.25 (mg/dL) ^‡

AHRQ: 9

Narendra et al., 2018 [27]

Asia (India)

Unknown

Cross-sectional

AAP criteria

NM

78 (40/38) vs. 50 (33/17)

38.34 ± 12.08 vs. 36.56 ± 6.26

CAL: 4.60 ± 0.51 vs. 1.49 ± 0.25

Blood/Serum

EBCM

5.10 ± 0.31 vs. 5.11 ± 0.54 (mg/dL)

AHRQ:6

Sreeram et al., 2015 [60]

Asia (India)

Unknown

Cross-sectional

 ≥ 14 teeth; BOP + at ≥ 30% periodontal sites with PPD = 1–3 mm; BOP + and CAL ≥ 3 mm at ≥ 30% of all sites

 ≥ 14 teeth; BOP + at < 30% sites with PPD = 1–3 mm; BOP + and CAL ≥ 3 mm at < 30% of all sites

150 (114/36) vs. 150 (120/30)

41.0 ± 12.2 vs. 34.2 ± 12.0

NM

Blood/Serum

EBCM

4.29 ± 1.15 vs. 4.93 ± 0.87 (mg/dL)

AHRQ:7

Brotto et al., 2011 [52]

South America (Brasil)

University

Case control

 ≥ 14 teeth including third molars; at least 4 different teeth had at least one site with PPD = 3–5 mm, and at least 4 others different teeth had at least one site with PPD = 6–10 mm; the proportion of all sites were considered to be AL > 2 mm and PPD > 2 mm

 ≥ 14 teeth including third molars; BOP + at < 30% sites with PPD = 1–3 mm, only 2 isolated sites with PPD = 4 mm and BOP-, and CAL ≥ 3 mm at < 30% of all sites

30 (16/14) vs. 30 (16/14)

46 ± 6 vs. 43 ± 5

PPD: 2.25 (1.39–3.62) vs. 1.00 (1.00–1.40) CAL: 2.58 (1.45–4.50) vs. 1.00 (1.00–2.27)

Blood/Serum

EBCM

4.9 ± 2.1 vs. 4.3 ± 1.7 (mg/dL)

NOS:6

Tsai et al., 2021 [22]

Asia (China)

National institutions

Cross-sectional

Localized stage II/III periodontitis

Periodontally healthy or stage I periodontitis

295(269/26) vs. 828(726/102)

30.88 ± 5.35 vs. 29.38 ± 5.56

PPD: 3.03 ± 0.04 vs.2.92 ± 0.05 CAL: 3.07 ± 0.06 vs. 2.93 ± 0.06

Blood/Serum

EBCM

6.73 ± 1.45 vs. 6.49 ± 1.41 (md/dL)

AHRQ:7

Sakanaka et al., 2017 [57]

Asia (Japan)

University

Case control

PISA > 215

PISA < 215

35 vs. 15

NM

PISA: 490.8 (200.5–1238.5) vs. 199.3 (155.5–252.8)

Saliva/Resting

Gas Chromatography—Mass Spectrometry

112.32 ± 66.02 vs. 155.83 ± 82.69 (Intensity)^§?

NOS:6

Novakovic et al., 2014 [56]

Europe (Serbia)

National institutions

RCT

 ≥ 3 teeth per quadrant; at least one pocket PPD > 5 mm with BOP + per quadrant; and ABL > 30%

Periodontally healthy

42 (28/14) vs. 21 (14/7)

39.0 ± 11.81 vs. 35.2 ± 7.1

PPD: 3.38 ± 0.58 vs. 2.11 ± 1.67; CAL: 3.00 ± 1.00 vs. 0

Saliva/Resting

EBCM

153.93 ± 40.88 vs. 198.43 ± 87.73 (relative level)

NOS:6

Miricescu et al., 2014 [28]

Europe (Romania)

National institutions

Cross-sectional

Gingival inflammation; at least six sites with PPD ≥ 4 mm; and ABL > 30%

NM

25 (11/14) vs. 25 (5/20)

51.26 ± 7.4 vs. 18.66 ± 2.0

PPD: 4.41 ± 0.42 vs. 0

Saliva/Resting

EBCM

2.41 ± 0.27 vs. 3.12 ± 0.85 (mg/mg albumin)

AHRQ:4

Mathur et al., 2013 [54]

Asia (India)

Unknown

Case control

CPITN > 2

CPITN ≤ 2

30 vs. 10

NM

NM

Saliva/Resting

EBCM

2.34 ± 0.4 vs. 5.19 ± 0.8 (relative level)

NOS:4

Fatima G et al., 2016 [53]

Asia (India)

Unknown

Case control

PPD = 6 mm or presence of CAL

No periodontal pockets as assessed by Williams periodontal probe

10 (4/6) vs. 10 (4/6)

46.30 ± 8.62 vs. 27.30 ± 4.37

NM

Saliva/Resting

EBCM

3.01 ± 0.68 vs. 5.39 ± 1.49 (mg/dL)

NOS:7

Sharma et al., 2018 [59]

Asia (India)

Nil

Cross-sectional

Russell’s periodontal index and a panoramic radiograph

Russell’s periodontal index, and a panoramic radiograph

25 vs. 25

34.32 vs. 30.68

NM

Saliva/Resting

EBCM

1.95 ± 0.42 vs. 3.72 ± 1.02(mg/dL)

AHRQ:7

Senouci et al., 2021 [58]

Africa (Algeria)

University

Case control

stage III– IV, grade C periodontitis

without clinical signs of periodontal disease as measured by PPD or any CAL

29 (6/23) vs. 28 (7/21)

24.06 ± 6.09 vs. 24.73 ± 1.38

PPD: 7 ± 1.68 vs. 1.7 ± 0.3; CAL: 7.81 ± 1.79 vs. 1.4 ± 0.2

Saliva/Resting

EBCM

1.43 ± 0.93 vs. 2.78 ± 1.60(mg/dL)

NOS:8

Priya, K.L., et al., 2022 [61]

Asia (India)

University

Case control

Stage II/III, grade B periodontitis

PPD ≤ 3 mm, without attachment loss or radiographic bone loss

20 vs. 20

30–65

PPD: 5.10 ± 0.26 vs. 1.36 ± 0.27 CAL: 5.47 ± 0.23 vs. 1.35 ± 0.27

Saliva/Resting

EBCM

5.64 ± 4.32 vs. 21.49 ± 10.01(mg/dL)

NOS: 6

Diab-Ladki et al., 2003 [29]

Asia(Lebanon)

National institutions

Case control

Severe periodontitis (with tooth mobility, gingival recession and up to one-half of ABL)

Apparently healthy gingiva

17 vs. 20

30–45

NM

Saliva/Stimulated

EBCM

2.41 ± 2.32 vs. 2.68 ± 2.46 (mg/dL) ^‡§?

NOS:2

Narendra et al., 2018 [27]

Asia (India)

Unknown

Cross-sectional

AAP criteria

NM

78 (40/38) vs. 50 (33/17)

38.34 ± 12.08 vs. 36.56 ± 6.26

CAL: 4.60 ± 0.51 vs. 1.49 ± 0.25

GCF/Paper strip

EBCM

4.87 ± 0.36 vs. 5.11 ± 0.53 (mg/dL)

AHRQ:6