Azuma, T.; Yamane, M.; Ekuni, D.; Kawabata, Y.; Kataoka, K.; Kasuyama, K.; Maruyama, T.; Tomofuji, T.; Morita, M.
Source: Antioxidants, Volume 4, Issue 3 (2015)

Background:
Oxidative stress plays a role in the pathogenesis of periodontitis. Reducing oxidative stress through the consumption of hydrogen-rich water (HRW) may provide benefits for periodontal health.

Objective:
This pilot study aimed to compare the effects of non-surgical periodontal treatment with and without HRW consumption on periodontitis.

Methods:
Thirteen patients with periodontitis (3 females and 10 males) were divided into two groups: a control group (n = 6) and an HRW group (n = 7). Participants in the HRW group consumed HRW 4–5 times daily over an eight-week period. All participants received non-surgical periodontal treatment between weeks 2 and 4. Oral examinations and serum samples for oxidative stress evaluation were conducted at baseline, and after 2, 4, and 8 weeks.

Results:
At baseline, there were no significant differences in periodontal status between the two groups. The HRW group exhibited greater improvements in probing depth and clinical attachment level compared to the control group at 2, 4, and 8 weeks (p < 0.05). Additionally, the HRW group showed a significant increase in serum total antioxidant capacity after four weeks compared to baseline (p < 0.05).

Conclusion:
Drinking hydrogen-rich water enhanced the effects of non-surgical periodontal therapy, contributing to the improvement of periodontitis.

Citation:
Azuma, T., Yamane, M., Ekuni, D., et al. (2015). Drinking hydrogen-rich water has additive effects on non-surgical periodontal treatment of improving periodontitis: A pilot study. Antioxidants, 4(3), 513–522.
https://doi.org/10.3390/antiox4030513

Kasuyama, K.; Tomofuji, T.; Ekuni, D.; Tamaki, N.; Azuma, T.; Irie, K.; Endo, Y.; Morita, M.
Source: Journal of Clinical Periodontology, Volume 38, Issue 12 (2011)

Background:
Reactive oxygen species (ROS) contribute to the development and progression of periodontitis. Given that molecular hydrogen acts as a scavenger of ROS, this study investigated the effects of hydrogen-rich water (HRW) on periodontitis in a rat model.

Methods:
Ligatures were placed around the maxillary molars of rats for four weeks to induce periodontitis. The animals received drinking water either with or without dissolved hydrogen.

Results:
Rats with ligature-induced periodontitis that received pure water exhibited a time-dependent increase in serum ROS levels. Compared to healthy controls, these rats also showed polymorphonuclear leukocyte infiltration and alveolar bone loss after four weeks. HRW administration inhibited the rise in serum ROS and reduced the expression of 8-hydroxydeoxyguanosine and nitrotyrosine in periodontal tissues. These outcomes were associated with suppression of leukocyte infiltration and osteoclast differentiation during the progression of periodontitis. Furthermore, inflammation-related signalling pathways—such as mitogen-activated protein kinases (MAPKs)—were less activated in periodontal lesions of HRW-treated rats compared to those treated with pure water.

Conclusion:
Consumption of hydrogen-rich water may be beneficial in suppressing the progression of periodontitis by reducing oxidative stress in the gingival tissues.

Citation:
Kasuyama, K., Tomofuji, T., Ekuni, D., Tamaki, N., Azuma, T., Irie, K., Endo, Y., & Morita, M. (2011). Hydrogen-rich water attenuates experimental periodontitis in a rat model. Journal of Clinical Periodontology, 38(12), 1085–1090.
https://doi.org/10.1111/j.1600-051X.2011.01801.x

Zhao, Y.W.; Zhou, Z.L.; Li, S.M.; Schmalz, G.; He, L.; Sun, C.C.; Yang, Y.Y.; Zhao, R.; Wang, J.M.; Liu, S.Y.; Zhang, Y.; Xiong, J.
Source: Journal of Biological Regulators and Homeostatic Agents, Volume 37, Issue 12 (2023)

Background:
Hydrogen-rich water (HRW) is widely used for its antioxidant and anti-inflammatory properties to mitigate inflammatory responses in various diseases. However, its efficacy in the treatment of peri-implantitis remains unclear.

Objective:
This study aimed to evaluate the effectiveness of HRW in reducing inflammation in a model of experimental peri-implantitis.

Methods:
An experimental peri-implantitis model was established in three Beagle dogs using ligature-induced inflammation around 24 implants. The implants were divided into two groups: an HRW-treated group (n = 12 implants) and an untreated control group (n = 12 implants). Clinical indices were evaluated, including the Gingival Index (GI), modified Sulcus Bleeding Index (mSBI), and probing depth (PD). Haematoxylin and eosin (H&E) staining was performed to assess inflammatory cell infiltration in peri-implant tissues. Levels of three host-derived pro-inflammatory cytokines—interleukin-1 (IL-1), interleukin-6 (IL-6), and matrix metalloproteinase-8 (MMP-8)—were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, microbial community profiles were analysed using high-throughput sequencing (HTS).

Results:
No statistically significant differences in GI were observed between the two groups at weeks 0, 2, and 4 (all p > 0.05); however, by week 6, the GI in the HRW group was significantly lower than in the control group (p = 0.005). No significant differences in PD were observed at any time point (all p > 0.05). Regarding mSBI, there were no initial differences at baseline (p > 0.05), but the HRW group showed significantly lower scores at weeks 2, 4, and 6 compared to the control group (p = 0.008, p = 0.005, p = 0.001, respectively). The HRW group also exhibited significantly fewer inflammatory cells and lower levels of IL-1, IL-6, and MMP-8 (p < 0.05). Moreover, there was a notable reduction in the relative abundance of pathogenic bacterial species, including Porphyromonas gingivalis, Fusobacterium nucleatum, Fusibacter, and Fretibacterium (p < 0.05).

Conclusion:
Within the scope of this study, the application of hydrogen-rich water showed promise and effectiveness in the treatment of peri-implantitis, supporting its potential as a therapeutic strategy for managing peri-implant inflammation.

Citation:
Zhao, Y.W., Zhou, Z.L., Li, S.M., et al. (2023). Hydrogen-rich water for the treatment of experimental peri-implantitis. Journal of Biological Regulators and Homeostatic Agents, 37(12), 7021–7033.
https://doi.org/10.23812/j.biol.regul.homeost.agents.20233712.663

Yoneda, T.; Tomofuji, T.; Kunitomo, M.; Ekuni, D.; Irie, K.; Azuma, T.; Machida, T.; Miyai, H.; Fujimori, K.; Morita, M.
Source: Nutrients, Volume 9, Issue 1 (2017)

Background:
Obesity induces oxidative stress in gingival tissues, which contributes to the progression of alveolar bone resorption. The antioxidant properties of hydrogen-rich water (HRW) may alleviate gingival oxidative stress and help prevent alveolar bone loss associated with obesity.

Objective:
This study aimed to determine whether HRW could suppress gingival oxidative stress and alveolar bone resorption in obese rats fed a high-fat diet.

Methods:
Eighteen male Fischer 344 rats were divided into three groups (n = 6 per group): a control group (fed a standard diet and distilled water), and two experimental groups (fed a high-fat diet with either distilled water or HRW). Gingival oxidative stress was evaluated by measuring 8-hydroxydeoxyguanosine (8-OHdG) levels. Alveolar bone mineral density was assessed using micro-computed tomography.

Results:
Rats fed a high-fat diet showed elevated levels of 8-OHdG in gingival tissues and decreased alveolar bone density compared to the control group. HRW intake suppressed body weight gain, reduced gingival 8-OHdG levels, and decreased alveolar bone resorption in the high-fat diet group.

Conclusion:
These findings suggest that hydrogen-rich water may attenuate gingival oxidative stress and alveolar bone resorption by mitigating obesity-related effects.

Citation:
Yoneda, T., Tomofuji, T., Kunitomo, M., et al. (2017). Preventive effects of drinking hydrogen-rich water on gingival oxidative stress and alveolar bone resorption in rats fed a high-fat diet. Nutrients, 9(1), 64.
https://doi.org/10.3390/nu9010064

Tomofuji, T.; Kawabata, Y.; Kasuyama, K.; Endo, Y.; Yoneda, T.; Yamane, M.; Azuma, T.; Ekuni, D.; Morita, M.
Source: Scientific Reports, Volume 4 (2014)

Background:
Oxidative damage is implicated in age-related inflammatory responses. The antioxidant properties of hydrogen-rich water (HRW) may help suppress oxidative damage, potentially contributing to the inhibition of age-associated inflammation.

Objective:
This study investigated the effects of HRW consumption on aging periodontal tissues in healthy rats.

Methods:
Twelve four-month-old male Fischer 344 rats were divided into two groups: an experimental group (treated with HRW) and a control group (treated with distilled water). The rats consumed either HRW or distilled water until the age of 16 months.

Results:
The experimental group exhibited reduced oxidative damage in periodontal tissues at 16 months of age compared to the control group. Although there was no difference in protein expression levels of interleukin-1 beta (IL-1β), the expression of the inflammation-related gene Nod-like receptor protein 3 (NLRP3) was elevated in periodontal tissues of the HRW group relative to controls.

Conclusion:
Hydrogen-rich water appears to exert anti-aging effects by reducing oxidative damage in periodontal tissues. However, it does not seem to influence inflammatory responses in healthy rats.

Citation:
Tomofuji, T., Kawabata, Y., Kasuyama, K., et al. (2014). Effects of hydrogen-rich water on aging periodontal tissues in rats. Scientific Reports, 4, 5534.
https://doi.org/10.1038/srep05534

Hadi, L.; Hutapea, A.M.; Florenly, F.
Source: The Indonesian Biomedical Journal, Volume 15, Issue 6 (2023)

Background:
Orthodontic tooth movement (OTM) in patients with diabetes mellitus (DM) may increase the risk of treatment-related complications. Numerous studies have shown that hydrogen-rich water (HRW) can reduce oxidative stress and cellular damage.

Objective:
This study aimed to evaluate levels of interleukin-1β (IL-1β), blood glucose levels, body weight, tooth displacement, and populations of osteoclasts and osteoblasts in streptozotocin (STZ)-induced diabetic rats undergoing OTM.

Methods:
Thirty Rattus norvegicus rats were divided into six groups: OTM, HRW, DM, DM+OTM, DM+HRW, and DM+OTM+HRW. The DM, DM+OTM, DM+HRW, and DM+OTM+HRW groups were induced with STZ after 8 weeks on a high-fat diet (HFD) and continued HFD for an additional 4 weeks. The OTM, DM+OTM, and DM+OTM+HRW groups received orthodontic appliances for tooth movement. HRW, DM+HRW, and DM+OTM+HRW groups were administered HRW via oral gavage three times daily for 4 weeks. At the end of the study, all rats were sacrificed; blood samples were collected for IL-1β analysis using ELISA kits, and maxillae were harvested for measuring tooth movement and counting osteoclasts and osteoblasts.

Results:
The highest IL-1β levels were observed in the DM+OTM group (140.07 ± 5.14 pg/mL), while the lowest were in the HRW-only group (92.80 ± 2.89 pg/mL). Osteoblast counts were higher in tension sites, while osteoclast counts were greater in pressure sites.

Conclusion:
HRW consumption in STZ-induced diabetic rats undergoing OTM may reduce IL-1β levels, limit tooth mobility, and support bone remodelling.

Citation:
Hadi, L., Hutapea, A.M., & Florenly, F. (2023). Effects of Hydrogen-Rich Water on Interleukin-1β, Number of Osteoclasts and Osteoblasts in Streptozotocin-induced Diabetic Rats with Orthodontic Tooth Movement. The Indonesian Biomedical Journal, 15(6), 420–428.