Table 2.

Vitamins and Periodontal Diseases.

Nutrient(s)	Type of Study	Methodology	Follow-Up Period	Clinical Outcomes	Subclinical Outcomes	Author(s) and Year
Vitamin D	RCT	360 patients with moderate or severe periodontitis received nonsurgical periodontal treatment, and after 3 months were divided into 3 groups: 2000 IU/day of vitamin D3, 1000 IU/day of vitamin D3, and placebo. Periodontal parameters were evaluated at the beginning and end of treatment.	3 months	Vitamin D supplementation in both dose groups resulted in slight but significant reduction in PPD and CAL for moderate and deep periodontal pockets.	N/A	Weimin Gao et al., 2019 [29]
Vitamin D	RCT	37 periodontitis patients with serum vitamin D3 levels below 30 ng/mL were divided into 2 groups. Both groups received initial SRP treatment. Test group received 25,000 IU/week of vitamin D3 and control group received placebo for 6 months. Periodontal parameters were evaluated at 1, 3, and 6 months of treatment.	6 months	Test group showed better results in PPD reduction after treatment.	N/A	Marina Peri’c et al., 2020 [30]
Vitamin D	RCT	40 patients with periodontitis were divided into 2 groups. Both groups received SRP treatment. Test group received 400 IU/day for 6 weeks and control group did not. Periodontal parameters and serum vitamin D levels were evaluated before and after periodontal treatment, and after 6 weeks of vitamin D treatment.	6 weeks	Intragroup comparison of clinical parameters from baseline to 6 weeks showed a statistically significant reduction in both groups. No differences observed between comparison groups.	Bone mineral density was evaluated by a qualitative ultrasound; however, no significant difference was observed between comparison groups.	Shree Mohan Mishra et al., 2022 [31]
Vitamin D	RCT	19 patients with GAgP periodontitis received initial periodontal treatment. CGF collection was performed before therapy and after 2 and 6 months. Plasma collected before therapy and after 2 months to compare systemic and local levels of 25-hydroxyvitamin D3, osteocalcin, and interleukin-1b and -6 before and after treatment.	6 weeks	GCF levels of vitamin D3 and IL-1β decreased significantly from baseline to 2 and 6 months after therapy.	Systemic levels of vitamin D3 and IL-1β were reduced significantly from baseline to 2 months after therapy.	Kaining Liu et al., 2010 [32]
Vitamin D	Pilot RCT	23 patients with dark skin were randomized into 2 groups. Test group received 4000 IU/day of vitamin D and control group received placebo for 8 weeks, after which time both groups received SRP and continued to use their supplements for another 8 weeks. At 8 and 16 weeks, saliva was collected to assess the presence of inflammatory cytokines.	16 weeks	Test group showed reduction in cytotoxic T lymphocytes (CD3 and CD8) in the blood and reduced salivary cytokines, but increased proteins related to autophagy.	N/A	Mohamed M. Meghil et al., 2019 [33]
Vitamin C	RCT	30 patients with periodontitis were divided into 2 groups. Both groups received SRP treatment. Test group received vitamin C. Periodontal parameters and plasma antioxidant capacity (TAOC) levels were evaluated at the beginning and end of treatment.	4 weeks	There was no effect on clinical periodontal parameters after treatment; only 20% of the periodontitis patients were vitamin-C- depleted (plasma concentration < 4 mg/L).	TAOC levels were lower in patients with periodontitis after treatment.	Ali E. Abou Sulaiman et al., 2010 [34]
Vitamin C and Omega-3	Case-Control	Periodontitis patients: total number N = 373 were further divided into: 245 periodontitis without tooth loss (POL) and 128 periodontitis with tooth loss (PWL). They were matched to 373 controls. Food Frequency Questionnaire was used to collect data on vitamin and omega-3 fatty acid intake, as well as their dental status. Blood samples were collected for metabolite concentrations analysis.	Not specified	Not specified	Higher intake of vitamin C in periodontitis group (p = 0.007) compared to control. Periodontitis with tooth loss showed a significantly elevated daily vitamin C intake compared to control (p = 0.02). No significant difference between the groups in the total uptake of omega-3 fatty acids.	Mewes et al., 2022 [35]
Vitamin E	RCT	38 patients with periodontitis were divided into 2 groups. Both groups received SRP treatment. Test group received 200 mg of vitamin E every other day for 3 months. Periodontal parameters and salivary superoxide dismutase (SOD) activity were evaluated before and after treatment.	3 months	Test group showed better results in all analyzed periodontal parameters (PPD, BOP, PI, GI, CAL) after treatment.	Test group showed better results in salivary superoxide dismutase (SOD) activity after treatment.	Neha Singh et al., 2013 [36]
Vitamin C, E, lysozyme and carbazochrome	RCT	100 patients were divided into 2 groups. Test group received a fixed dose of the combination of vitamin C, vitamin E, lysozyme, and carbazochrome (CELC) combined with SRP, and control group received SRP and placebo for 4 weeks. Both groups received vitamins for another 4 weeks. Periodontal parameters were evaluated at 4 and 8 weeks.	8 weeks	Test group showed GI reduction after 4 and 8 weeks, but without any differences in other periodontal parameters between studied groups.	N/A	Ji-Youn Hong et al., 2019 [37]
Folic Acid	RCT	60 patients with periodontitis were divided into 2 groups. Both groups received initial SRP. Test group received folic acid and control group received placebo 3x/day for 4 weeks. Periodontal parameters and crevicular fluid were assessed at baseline and after 1, 3, and 6 months.	4 weeks	Significant time-dependent reduction was detected in all clinical parameters for both groups. Test group showed better results in CAL at months 1 and 3, and in GI at month 1.	Test group showed more homocysteine (Hcy) at months 3 and 6. GCF and Hcy volume showed reduction after treatment in both groups.	Keceli et al., 2020 [38]
Micronutrient complex	RCT	30 patients with periodontitis adhered to the Mediterranean diet and SRP treatment and took a micronutrient complex or olive oil twice a day for 3 months. Periodontal parameters were correlated with serum C-reactive protein and MMP-8/9 salivary matrix, quantified at 1 and 3 months of treatment.	3 months	Both groups showed better periodontal parameters at all time points. No differences between studied groups.	SRP and micronutrient complex resulted in reduction in salivary MMP-8/-9 at T2, and of MMP-9 at T1, while SRP and olive oil did not induce any significant changes in MMP-8/-9.	Giulio Rasperini et al., 2019 [39]
Collagen peptide	RCT	39 periodontal recall patients with history of treated periodontitis were divided into 2 groups. Test group received sachets containing a specific preparation of collagen peptide and control group received placebo 1 time/day for 90 days. Both groups received professional mechanical debridement.	3 months	The addition of collagen peptide showed better results in BoP, PISA, and GI after treatment compared to placebo after professional mechanical debridement.	N/A	Yvonne Jockel-Schneider et al., 2022 [40]
Nutraceutical agent (Neuridase®, Enfarma SRL, Misterbianco, Italy)	RCT	66 patients with moderate periodontitis were divided into 2 groups. Test group received nutraceutical agent and SPR while control group received SRP and placebo.	6 months	Test group showed better results in periodontal parameters (PPD, BOP, CAL) after 30 and 60 days compared to control group.	Test group showed greater reduction in inflammatory mediators, and change in pain (VAS) 6, 12, 24, and 48 h after SRP.	Gaetano Isola et al., 2021 [41]

Abbreviations: RCT: Randomized controlled trial; PPD: Probing pocket depth; CAL: Clinical attachment level; SRP: Scaling and root planing; GCF: Gingival crevicular fluid; BOP: Bleeding on probing; GI: Gingival index; PI: Plaque index; PISA: Periodontal inflamed surface area; VAS: Visual analogue scale; MMP: Matrix metalloproteinase; IL: interleukin; N/A: Not available.