Association between retinol intake and periodontal health in US adults

Periodontitis is a common chronic inflammatory disease caused by oral biofilm infection, which leads to the progressive destruction of surrounding periodontal tissue [1]. Recent epidemiological evidence indicates that 35% of the general US population suffers from periodontitis, of which approximately 10% are in severe stages [2]. In addition, periodontitis increases the risk of multiple systemic diseases, such as cardiovascular disease and diabetes mellitus [3]. Although there are a growing number of influencing factors for periodontitis, such as flap design [4], few of them can be changed. Thus, it is necessary to identify modifiable influencing factors to improve understanding of periodontitis pathology and facilitate more cost-effective public health efforts targeting periodontitis [5].

Nutrition is an important modifiable factor for periodontitis. For example, pro-inflammatory diets increase the risk of periodontitis, indicating that modulating dietary inflammatory potential may be a useful strategy for the prevention and treatment of periodontal disease [6]. In addition to inflammation, oxidative stress induces proinflammatory mechanisms and osteoclastogenesis, leading to alveolar bone resorption in periodontitis patients [7]. Thus, nutrition with anti-inflammatory and antioxidant capabilities may reduce the risk of periodontitis. Retinol, the active form of vitamin A, is an antioxidant that could scavenge free radicals, inhibit peroxidation and sustain the homeostasis between oxidants and antioxidants [8]. Retinol also has anti-inflammatory ability. For example, it impedes the expression of various proinflammatory cytokines, such as TNF-α, IL-6, IL-12, etc. [9]. Furthermore, retinol has the potential to involve in periodontal reparative. In detail, retinol affects the proliferation and differentiation of the gingival mesenchymal stem [10]. Although the role of retinol has been explored in vitro, the association between retinol intake and periodontists is poorly understood in cross-section study.

Thus, this study aimed to assess the relationship between retinol intake and periodontitis after adjusting for potential confounders based on data from National Health and Nutrition Examination Survey (NHANES). We also explored this association in different subgroups.

In this cross-sectional study, we found that retinol intake was inversely associated with moderate/severe periodontitis in the US adult population. In addition, such association remained significant in populations who were less than 60 years old, non-Hispanic black, PI ≤ 1.3, 1.3 < PI ≤ 3.5, non-smoker, obesity and who had not diabetes mellitus or had hypertension. Our study offers a potential new strategy for the prevention and treatment of periodontal disease.

Oxidative stress is a hallmark of multiple diseases, including periodontitis. Recent study indicates that human gingival fibroblasts from periodontitis exhibits enhanced ROS production [12]. ROS has been regarded as a “double-edged” sword in periodontitis. ROS is produced by neutrophils to eliminate invading pathogenic microorganisms in healthy periodontal tissue, however, excessive ROS can trigger cytotoxic to host cells by damaging DNA, lipids and proteins [13]. Thus, it is necessary to reduce ROS production to improve the prognosis of periodontitis. Antioxidant compounds, such as resveratrol and curcumin, inhibit osteoclastogenesis and reduce alveolar bone loss, and thus they have the potential to provide additional benefits for scaling and root planning [7]. In addition, dietary or nutritional interventions show favorable effects on periodontal treatment outcomes and prevention of periodontitis [14]. For example, supplementation of vitamin C can decrease the risk of periodontitis and suppress the senescence of periodontal ligament stem cells [15‐17]. However, the association between periodontitis and intake of another antioxidant, retinol, is unclear.

Retinol, the active form of vitamin A, must be obtained from the diet and is involved in diverse biological functions, including proliferation, apoptosis, differentiation and metabolism [18]. Mammalian cells uptake retinol via STRA6 and retinol can be metabolized to retinal and then retinoic acid [19]. Retinoic acid exhibits inhibition of periodontal inflammation. In detail, an oral supplement of all-trans retinoic acid in periodontitis mouse model suppresses inflammatory cell infiltration and Th17 cell activation and enhances Treg cell activation, thereby reducing alveolar bone loss [20].

In addition, retinol itself might hamper progression of periodontitis. It reduces the expression of serval inflammatory factors such as TNF-β, IL-6, IL-1α and IL-1β [21, 22]. Most importantly, retinol has the ability to drive cellular de-differentiation and pluripotency [23], which is vital to periodontal tissue regeneration. Thus, it is reasonable to find that higher retinol intake reduces the risk of periodontitis.

In line with our results, in young Korean women, a marginal association between lower retinol intake and periodontitis is found (OR = 1.56, 95% CI: 1.00–2.44) [24]. However, such association is not observed in men aged 60–70 from Northern Ireland [25]. In our study, we also did not find association between retinol intake and periodontitis in population over the age of 60. This might be because aging is a risk factor of periodontitis, increasing prevalence and progression of periodontitis [26]. Thus, it is still necessary to seek other modifiable influencing factors for elderly patients with periodontitis.

In subgroup analysis, we found that retinol intake was inversely associated with moderate/severe periodontitis in serval groups, such as non-Hispanic black, non-smoker and obesity. Bacterial composition in periodontal tissue might partly account for this result. Metagenomics indicates that smoking, geographical location and ethnicity play an important role in bacterial composition. For example, oral biofilm in smokers consists of more periodontopathogen bacteria compared to non-smokers [27].

It has demonstrated that periodontitis was associated with multiple systemic diseases, including cardiovascular disease. Anticoagulant drugs are common for cardiovascular disease and thus increase the risk of periodontal treatment in these patients [28]. Previous studies indicate that all-trans retinoic acid could ameliorate the coagulopathy. In detail, all-trans retinoic acid reduces plasma levels of fibrinopeptide A, prothrombin fragment 1.2, thrombin antithrombin complex and fibrin d-dimer [29]. Thus, retinol intake may not be appropriate for patients with cardiovascular disease who are about to undergo periodontal treatment.

Our study has several limitations. First, it is unfeasible to identify causal relationships between retinol intake and periodontitis based on cross-sectional designs. Future multi-center prospective trails are required to corroborate the potential causal association and help confirm the benefits of increasing retinol intake on periodontitis health. Second, two 24-h diet recall interviews may not be ideal for reflecting long-term dietary intake. Finally, we could not rule out all possible residual confounders due to unmeasured confounding factors.

Retinol intake is inversely associated with periodontitis among US adults. Further prospective trials are required to support our findings.