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. 2018 May 20;23(5):1226. doi: 10.3390/molecules23051226

Table 5.

Observational studies on vitamin C association with periodontal disease.

Study Type Sample Sex; Age; N Dietary Intake Assessment Nutritional Status Assessment Periodontal Status Analysis Results (p-Value) Main Results/Conclusions Ref
CS NHANES III Participants (US) Both; ≤20 y; N = 12,419 Dietary intake by 24-h recall (0–29, 30–59, 60–99, 100–179, & ≥180 mg) - Periodontal disease 3 OR 1 = 1.28 (95%CI: 1.02–1.43); p < 0.05 for trend (mult. logistic reg.) in current smokers Negative association in smokers, it was stronger in former smokers than current tobacco users [69]
OR 1 = 1.21 (95%CI: 102–1.43); p < 0.05 for trend (mult. logistic reg.) in former smokers
CS NHANES III participants (US) Both; ≤20 y; N = 11,480 - Serum levels (quintiles) Mild periodontitis 4 OR 2= 0.82 (95%CI: 0.76–0.87); p = 0.0001 (mult. logistic reg.) in non-restricted model Negative association, it was stronger with severe disease, & in never-smokers [38]
OR 2= 0.71; (95%CI: 0.58–0.86); p = 0.001 for trend (mult. logistic reg.) in model restricted to never-smokers
Severe periodontitis 5 OR 2 = 0.76 (95%CI: 0.69–0.84); p = 0.0001 for trend) in non-restricted model
OR 2= 0.8 (95%CI: 0.71–0.89); p = 0.0001 for trend (mult. logistic reg.) in model restricted to never-smokers
CS Niigata study participants (Japan) Both; 70 y; N = 413 - Serum levels CAL β = −0.04 (95%CI: −0.06 to −0.005); p < 0.05 (mult. linear reg.) Negative association [77]
CS Dental clinic patients (US) Both; N.A.; N = 80 Dietary intakes by 24-h recall Serum levels RPI N.S. (mult. linear reg with R2 improvement) No associations [36]
CS NHANES participants (Japan) Both; ≥20 y; N = 3043 Dietary intake by 24-h recall - CPI = 3–4 N.S. (mult. logistic reg.) No associations [65]
CS Men from 2 populations (Finland & Russia) Male; 48.2 ± 13.6/44.8 ± 11.4 y; N = 431 - Plasma levels Serum IgG against Pg r = −0.22; p < 0.001 (Pearson correlation analysis) Negative association with anti-Pg IgGs level [73]
Serum IgG against Agact N.S. (Pearson correlation analysis)
CS Cancer-free individuals from an EPIC sub-cohort (Europe) Both; 35–70 y; N = 395 Dietary intake * - Total IgGs levels for 25 oral bacteria 6 N.S. (generalized linear models) No association [74]
CC Non-smokers outpatients (India) Both; 30–60 y; N = 60 - Serum levels DM2 & periodontal disease-affected7 only periodontal disease-affected & healthy 0.93 (±0.24) > 0.335 (±0.5) > 0.292 (±0.004); p < 0.001 (student t test) Subjects with periodontal disease showed lower vitamin C levels [72]
CC Patients from an academic center (NL) Both; ≥21 y; N = 42 - Levels in plasma Periodontitis-affected 8 vs. healthy 8.3 (±3.9) < 11.3 (±5.2) mg/L; p = 0.03 (N.A.) Subjects with periodontitis showed lower plasma levels of vitamin C [70]
No. of servings (of ≥31, 30 to 2, or <2 mg per 100 mg) by 3-d record N.S. differences
Total intake by 3-d record N.S. differences
CC Non-smokerss adolescents (Italy Female; 17–19 y; N = 56 Dietary intake by 3-d record - Gingivitis affected 9 vs. non-affected N.S. differences (Student t test) No association [37]
Dietary intakes marginal deficiency (<2/3 RDA) by 3-d record N.S. differences (X2 test)
RC (2 y) Niigata study participants (Japan) Both; 73 y; N = 264 Dietary intake (tertiles) by BDHQ - No. of teeth with periodontal disease progression 10 IRR 2 = 0.72 (95%CI: 0.56–0.93); p < 0.05 for trend (mult. logistic reg.) Negative association [41]
C (8 y) Niigata study participants (Japan) Both; 71 y; N = 224 - Serum levels (tertiles) Periodontal disease events 11 RR 2 = 1.30 (95%CI: 1.16–1.47); p < 0.05 for trend (mult. logistic reg.) Negative association [77]
RC (3 y) Residents from a village (Indonesia) Both; 33–43 y; N = 123 - Plasma levels (>2; 2–3.9; or ≥4.0 mg/L) Mean CAL β = −0.199; p = 0.029 (mult. linear reg.) Negative association [72]
C (10 y) NHEFS & NHANES I participants (US) Both; 25–74 y; N = 10,523 Dietary intake (% NHANES standards) by 24-h recall & FFQ - Total teeth lost β = −0.0031 (±0.0011); p = 0.01 (mult. linear reg.) in 25–59 y old subjects Negative association only in younger subjects [76]
N.S. (mult. linear reg.) in 60–74 y old subjects

1 values compared lowest vs. highest percentile, 2 values compared highest vs. lowest percentile, 3 mean CAL ≥1.5 mm, 4 ≥1 site with CAL ≥4 mm & PPD ≥4 mm, 5 ≥2 mesiobuccal sites with CAL ≥5 mm & 1 mesiobuccal sites with PPD ≥4 mm, 6 Pg ATCC 33277 & ATCC 53978, Agact ATCC 29523 & ATCC 43718, Tannerella forsythia ATCC 43037, Fusobacterium nucleatum ATCC 25586, Fusobacterium periodontium ATCC 33693, Fusobacterium polymorphum ATCC 10953, Prevotella intermedia ATCC 25611, Prevotella melaninogenica ATCC 25845, Prevotella nigrescens ATCC 33563, Veillonella atypica ATCC 17744, Veillonella parvula ATCC 10790, Bifidobacterium dentium ATCC 27534, Corynebacterium matruchotii ATCC 14266, Enterococcus faecalis ATCC 29212, Parvimonas micra ATCC 33270, Peptostreptococcus anaerobius ATCC 27337, Streptococcus intermedius ATCC 27335, Streptococcus mitis ATCC 49456 & Streptococcus salivarius ATCC 7073, 7 generalized CAL ≥5 mm & BOP, 8 ABL >1/3 of the root length in >1 tooth per quadrant, 9 ≥1 site with BOP, 10 CAL ≥3 mm in ≥1 site, 11 No. of teeth with a loss of CAL ≥3 mm. Abbreviations: 95%CI: 95% confidence interval, Agact: Aggregatibacter actinomycetemcomitans, BOP: Bleeding on probing; C: Cohort study, CAL: Clinical attachment level, CC: Case-control study, CEJ: Cementum-emanel junction, CS: cross-sectional study, EPIC: European Prospective Investigation into Cancer and Nutrition, DM1: Diabetes mellitus type 1, DM2: Diabetes mellitus type 2, FBG: Fasting blood glucose, FFQ: food frequency questionnaire, IgG: Immunoglobulin G, IRR: Incidence rate ratio, IWCPDC: International Workshop for the Classification of Periodontal Diseases & Conditions in 1999, NHANES I: First National Health and Nutrition Examination Survey, NHANES III: Third National Health and Nutrition Examination Survey; NHEFS: NHANES I Epidemiologic Follow-up Stud, NL: Netherlands, OR: Odds ratio; Pg: Porphyromonas gingivalis, PBMC: Peripheral blood mononuclear cells, PI: Plaque index; PMN: Polymorphonuclear neutrophils, PPD: Periodontal probing depth; RBG: Random blood glucose, Russell’s periodontal index; RR: Relative risk, US: Unite States, vs.: versus, y: years. * by extensive quantitative dietary questionnaires or semi-quantitative FFQ or combined food records & questionnaires quartiles.