The role of micronutrients in periodontal disease prevention and therapy

Vitamins

Vitamin C (ascorbic acid, AA) plays an important role in collagen synthesis, helps maintain the structural integrity of connective tissue, and has a protective effect on maintaining tissue homeostasis. It is a water-soluble antioxidant that neutralizes oxidative stress and is depleted in this process. AA deficiency has been considered a systemic risk factor among diet-related diseases that can modify the immuno-inflammatory response and has been included in the current (2018) classification of periodontal diseases agreed by the EFP and the American Academy of Periodontology.

Cross-sectional studies have found lower serum/plasma AA concentrations in patients with gingivitis or periodontitis, and in smokers, than in periodontally healthy individuals and non-smokers. An inverse relationship has been reported between plasma AA levels and the degree of periodontal inflammation as well as severity in different populations and age groups (Van der Velden et al. 2011). Furthermore, total antioxidant capacity has been associated with periodontitis while elevated serum antioxidant levels have reduced relative disease risk. Case-control studies have shown that periodontitis patients had lower AA plasma levels, lower AA intake, more bone loss, and greater periodontal disease progression than the healthy controls (Kuzmanova et al. 2012).

Other studies have shown that, while AA depletion resulted in gingival bleeding regardless of the level of individual oral hygiene, both the consumption of AA-rich fruits and AA supplementation had an inhibitory effect on sulcular bleeding in non-smoking patients with gingivitis and chronic periodontitis. However, this AA consumption or supplementation was less effective following periodontal nonsurgical interventions (Tada et al. 2019).

There are indications that the function of AA is superior when it is obtained from fruits rather than from dietary supplements. Fruits provide several additional micronutrients, phytochemicals, and dietary fibres that may influence the bioavailability of AA and have other beneficial effects.

Vitamin E comprises of a set of lipophilic antioxidant food compounds termed as α, β, γ, and δ tocopherols or tocotrienols. Their primary function, to protect cell membranes from reactive oxygen species and to regulate immune responses, has been widely studied (Shadisvaaran et al. 2021). While some epidemiological studies have observed an association between serum vitamin E concentration and periodontitis, others have not. Prospective studies have shown that higher vitamin E intake was associated with a lower number of teeth affected by periodontitis. Conversely, low serum alpha-tocopherol levels were associated with periodontal progression.

Intervention studies have suggested a positive effect of higher alpha-tocopherol intake on periodontal healing after subgingival instrumentation (scaling and root planing). The adjunctive intake of vitamin E has been shown to have significant beneficial effects on periodontal parameters as well as antioxidant defence compared to controls. Current literature suggests that vitamin E could improve periodontal status by correcting redox status imbalance, reducing inflammatory responses, and promoting wound healing. However, evidence from clinical trials is still limited.

Vitamin D is a fat-soluble micronutrient found only in small amounts in food and is a secosteroid hormone produced mainly by the skin when exposed to sunlight. Vitamin D plays an important role in calcium and bone metabolism. It is also thought to have immunomodulatory and anti-inflammatory effects. In patients with periodontitis, lower vitamin D levels compared with healthy controls have been reported. Higher serum 25-hydroxy vitamin D (25OHD) concentrations have been associated with lower rates of gingivitis and less attachment and tooth loss.

One prospective study reported that every 10 μL/L increase in serum 25OHD was associated with a 13% decrease in tooth loss, while another showed that Vitamin D supplementation after nonsurgical periodontal therapy resulted in a slight reduction in probing pocket depth (PPD) and attachment loss compared to placebo controls and improved anti-inflammatory response. Well-designed prospective and intervention studies are needed to define what plasma vitamin D concentration is required prior to the initiation of periodontal treatment to achieve the best therapeutic outcome.

The water-soluble B vitamins are involved in multiple processes, including metabolism, erythrocyte production, and collagen synthesis and they act as coenzymes in several enzymatic processes that support every aspect of cellular physiological functioning. Epidemiological data have demonstrated a higher severity of periodontal disease in individuals with inadequate dietary intake or serum levels of vitamin B9 (folate). Among patients with periodontal disease, smokers had lower serum folic acid concentrations than non-smokers. In a prospective cohort study, an increase in serum vitamin B12 was linked to a decrease in clinical periodontal parameters and tooth loss.

Giving a vitamin B-complex preparation to periodontitis patients after periodontal surgery has improved clinical attachment levels compared with patients receiving placebo. Furthermore, adjunctive systemic folate intake after subgingival instrumentation has resulted in significant additional gain in clinical attachment in patients with stage II-III periodontitis. Nevertheless, further clinical and biochemical data are needed to support these findings.

Vitamin A is a group of different lipid-soluble compounds (retinol, retinal, retinoic acid, provitamin A carotenoids) that play a crucial role in physiological processes such as cellular growth and differentiation, immune-system functioning, bone and foetus development, vision, and the formation of the central nervous system. Provitamin A carotenoids also act as antioxidants. Large-scale epidemiological studies have found either a weak or no association between vitamin A inadequacy and periodontitis and its efficacy in managing periodontitis progression is unclear (Dommisch et al. 2018). In contrast, higher dietary intake of β-carotene has been associated with a significantly lower percentage of sites with PPD >3mm after non-surgical treatment and a greater reduction in PPD in non-smokers than in smokers with periodontitis. Low serum carotenoid levels (α-, β-carotene, β-cryptoxanthin) have been associated with a significantly increased risk of periodontitis. In addition, a weak inverse relationship has been reported between the prevalence of mild periodontitis and serum concentrations of α-carotene, β-carotene and β-cryptoxanthin.

Lycopene, a pigment derived from red fruits, has been suggested to be one of the most effective in vitro singlet oxygen quenchers of the carotenoids. Research has shown that individuals with higher serum lycopene concentrations had reduced C-reactive protein (CRP) levels, while those with higher tomato consumption showed reduced leukocyte counts. An association between chronic periodontitis and an increased risk of heart failure has been suggested, with higher monthly tomato consumption reducing this risk in periodontitis patients. Intervention studies with a combined preparation of lycopene and other micronutrients (vitamins A, C, E, selenium, zinc) for oral application adjunctive to mechanical debridement have shown positive effects on periodontal healing.

Minerals and trace elements

Significant inverse relationships have been reported between serum/plasma levels of calcium, magnesium, zinc, and manganese and periodontal severity/progression.  Studies have shown that a low serum calcium-magnesium ratio is significantly associated with increased attachment loss and the progression of periodontal disease, and that individuals with periodontitis have a significantly lower dietary intake of calcium, magnesium, copper, selenium, and antioxidant nutrients – and respectively lower serum and saliva levels – compared to controls.

It has been suggested that milk and milk products – a source of calcium, phosphate, and various proteins – may have beneficial effects on periodontal health while, conversely, dietary calcium intakes below recommended reference levels have been associated with increased risk of tooth loss, severity of periodontal disease, and attachment loss.

Case-control studies have revealed significantly lower magnesium, selenium, and zinc levels in diabetic and non-diabetic patients with periodontitis compared to healthy controls. Other studies have shown non-surgical periodontal therapy leading to increased serum zinc levels in Type-2 diabetes mellitus patients with periodontitis, while subjects with magnesium supplementation have lower attachment loss and higher tooth retention compared to non-supplemented control subjects.

The current evidence on nutraceutical and food-based interventions as an adjunct to non-surgical periodontal therapy has been recently reviewed in a systematic review by Johan Peter Woelber and colleagues at the universities of Freiburg and Heidelberg in Germany (Woelber et al. 2023).

Diet and prevention

The prevention of non-communicable diseases (NCD) focuses on dietary changes to reduce the systemic inflammatory burden. A Western diet – rich in refined grains, red meat, high-fat dairy products, simple carbohydrates, and consumption of processed food – has been described as pro-inflammatory.

Cross-sectional data have indicated that a “high-quality” diet is identified as a health-promoting factor along with control of normal weight and adequate exercise. Participants who adhered to these three factors have shown a 40% lower risk of developing periodontitis. Nonetheless, the role of physical activity, weight loss, and dietary counselling is the focus of further research.

A pro-inflammatory diet and poor micronutrient intake have been linked to an increased risk of periodontal disease. In contrast, adherence to an anti-inflammatory dietary pattern “high micronutrient and fibre” has been linked to a lower risk of periodontitis and tooth loss.

Dietary anti-inflammatory interventions such as Mediterranean diet, the Okinawan-based Nordic Diet (OBND), and so-called Palaeolithic diets have resulted in reduced gingival inflammation despite constant – or even increasing – plaque accumulation. In patients with periodontitis and either metabolic syndrome or Type-2 diabetes mellitus, dietary change to a wholesome nutrition or OBND led to improvements in both the periodontal and systemic inflammatory parameters without providing professional oral hygiene. Fasting has also been shown to facilitate the reduction of periodontal inflammation.

The need for more research

In conclusion, there is increasing evidence of the overall importance of micronutrients on general and periodontal health. Furthermore, the dietary source of micronutrients needs to be considered in the context of favourable dietary patterns based on a wide variety of micronutrient-rich foods as well as putative interactions between various micronutrients. Future research is required to further elucidate the role of micronutrients in the prevention and treatment of periodontal disease. Prospective and clinical intervention studies may help to define causal relationships, potential intervention strategies, and future recommendations.

While this article reflects some of the important aspects regarding the role of micronutrients in the prevention of periodontal disease and in periodontal therapy, it does not claim to offer a complete picture, since putative relevant aspects – such as genetics, microbiology, micronutrient deficiencies, and adverse effects – could not be covered extensively .