3.1.4. Resveratrol

We found two animal studies that evaluated the effects of resveratrol intake on the osseointegration of titanium implants.

In 2018, Ribeiro et al. [42] demonstrated that supplementation of resveratrol led to an improvement in counter-torque and BIC in rats exposed to cigarette smoking, compared to rats exposed to cigarette smoking but receiving placebo. This finding seems quite relevant, considering that detrimental effects of smoking on oral health in terms of increased postoperative infections and marginal bone loss in patients receiving dental implants are well established [48–50]. Also, Casarin et al., in 2014 [43], demonstrated that resveratrol intake had positive effects on the biomechanical retention of the implants, because there were significantly higher average counter-torque values for implant removal in rats that received resveratrol.

#### 3.1.5. Mixtures of Micronutrients

Pimentel et al., in 2016 [44], evaluated the effects of a mixture of calcium, magnesium, zinc, and vitamin D on rats that received titanium implants. They found that there was no statistically significant difference among the counter-torque values for implant removal, bone volume, and BIC in the placebo group when compared to the micronutrient group.

Takahashi et al., in 2016 [45], evaluated the effects of supplementation with synthetic bone mineral (SBM), a mixture of calcium phosphate dihydrate and magnesium and zinc chlorides, on titanium implants in osteoporotic rats. They found significantly higher bone volume and lower bone surface ratio in the SBM group. Moreover, the trabecular thickness increased significantly from two to four weeks after implant insertion in treated group, while the improvement of the same parameters was not significant in the control group. Also, other histomorphometric parameters significantly improved in SBM group, such as the trabecular star volume, although the between-group difference in terms of trabecular number was not significant. Finally, rats receiving SBM showed enhanced bone formation, evaluated by micro-computed tomography (micro-CT), both at two and at four weeks compared to rats fed without SBM.

Also, Watanabe et al., in 2015 [46], evaluated the effects of SBM on osseointegration in rats. They found that pull-out strength in the treated group was six times higher than in the control group two weeks after implantation and twice higher at four weeks. The BMD in the SBM group was approximately double compared to the control group at two weeks and more than double at four weeks. BMD color imaging showed that the control group colors mainly ranged from blue to yellow at two and four weeks after implantation, while the SBM group mainly occupied the orange and red end of the spectrum at two and four weeks after implantation. Given that blue and light blue, green and yellow, and orange and red represent low, medium, and high BMD, respectively, the BMD color imaging indicated that peri-implant bone had a higher BMD in the SBM group than in the control group. Fluorescence microscopy imaging of the control group revealed no green fluorescence at two weeks after implantation. However, green fluorescence was clearly observed in the SBM group at two and four weeks after implantation, while irregular bands appeared around the implants in the control group at four weeks.

## *3.2. Vitamin C*

Li et al., in 2018 [47], evaluated the effects of vitamin C supplementation on four populations: patients receiving dental implants by guided bone regeneration (GBR), patients treated with Bio-Oss collagen, patients with chronic periodontitis receiving dental implants, and a control group without any bone grafting or periodontal disease. The authors found that vitamin C supplementation improved postoperative wound healing following dental implant surgery in patients with chronic periodontitis and in those treated with GBR or Bio-Oss collagen grafts. However, vitamin C supplementation was ineffective in decreasing the postoperative pain associated with dental implant surgery.
