With the aging population increasing due to advances in healthcare and living conditions, chronic inflammatory diseases such as periodontitis have also been on the rise. The prevalence of moderate to severe periodontitis among adults aged 65 and over was 47.2% (1). This is significant because periodontitis is a leading cause of tooth loss, which can cause both functional and psychological issues, affecting quality of life. Over the recent years, people have been making more effort to retain their teeth due to aesthetic and social reasons. Contrary to popular belief, periodontitis does not only affect the older population. Although prevalence varies due to bias, it affects 20%–50% of the global population, including developing and developed countries (2). In light of this, there is a need for increased awareness and education about the advent of periodontitis and the risk factors that contribute to it.

Periodontitis is a chronic and debilitating oral disease characterized by the inflammation and eventual destruction of the periodontal tissue, including the gingiva, alveolar bone, and cementum, which support the teeth (2). The disease is mainly caused by accumulated dental plaque and subsequent mineralization into calculus (tartar), which harbors pathogenic microorganisms. Periodontitis begins as gingivitis or gum inflammation, then forms pockets that progress apically to the alveolar bone. Around 800 species of bacteria are involved, producing many virulent toxins and enzymes that incite a chronic inflammatory response in the host, destroying the periodontal tissue and, if left untreated, tooth loss (2).

The etiology of periodontitis is multi-factorial and encompasses a range of risk factors, such as genetics, hormonal fluctuations, stress, and, most importantly, diet (3). Some of these factors are modifiable, including smoking, oral hygiene, and, to some extent, diet. These factors are worth looking into, as understanding their correlation with periodontitis can lead us to a step closer to prevention. Although a good deal of research has been conducted over the past few years regarding the relationship between smoking and periodontitis, little attention has been given to diet as a risk factor.

Studies from 2010 to 2023 were reviewed and analyzed. Databases used to search included PubMed, Mednet, Scopus, Cochrane, and Embase. The keywords used for the search included ((ketogenic diet) OR (keto diet)) AND (oral health). When typing keto diet OR Ketogenic diet AND periodontitis, the keywords showed only one result. We wanted to evaluate articles that mentioned the keto diet's significance in periodontitis conditions in their clinical trials. Hence, we used a broader terminology. The literature reviewed was limited to randomized clinical trials, observational studies, and case-control studies. Articles merely listing the advantages or disadvantages of the diet were excluded. Articles in English language only were selected. Narrative and systematic reviews were excluded. The review contained ten articles that were thoroughly read and analyzed (Figure 2).

The present study investigates the relationship between the ketogenic diet and periodontitis. The relationship between diet and periodontal health has recently become a point of interest, with many interventional studies confirming this link. Of the eight studies included, only two directly investigated the potential relationship between keto and periodontitis (15–17). Another pilot trial found no changes in periodontal health in subjects after following a 6-week ketogenic diet (18). Three studies found that diets similar to the ketone-based diet could significantly positively impact periodontal health (16, 19, 20). These include two randomized clinical trials in which subjects following an oral-health-optimized diet containing reduced carbohydrates showed decreased potential periodontal bacterial species in the supragingival oral plaque and decreased periodontal inflammation (19, 20). One study pointed to the potential positive effect of a diet such as keto, but no definitive conclusion could be made (18). Another RCT is associated with using sugar substitutes such as erythritol, commonly used in the keto diet as sugar is restricted, with reduced plaque growth (21). One study showed that the ketogenic diet has an anti-inflammatory effect, which could be necessary as periodontitis is a chronic inflammatory disease (16, 20) (Table 1).

Like most chronic diseases, periodontitis can be influenced by many external factors. Research suggests that environmental factors, genetics, epigenetics, and lifestyle choices could contribute to the development of periodontitis by influencing the composition of the biofilm and the host's inflammatory immune response (22).

Periodontitis has been described as an inflammatory disease mainly resulting from the invasion of both the innate and the adaptive immune systems. The development of bacterial biofilm, sometimes called dental plaque, on the teeth's surface initiates the disease process. Pathogenic and commensal microorganisms coexist in the complex and dynamic community known as the bacterial biofilm. The expanding bacterial biofilm produces many virulence factors, including lipopolysaccharides, proteases, and toxins, and can start and maintain the inflammatory response in the periodontal tissues (22).

Neutrophils, macrophages, and T lymphocytes are just a few immune cells drawn to the infection site as part of the host response to the bacterial attack. The cytokines and chemokines these immune cells release increase the inflammatory response, activating osteoclasts and bone resorption (9). The periodontal fibroblast is one of the primary cells in the pathophysiology of periodontitis. These cells are the primary cell type in the periodontal ligament and are critical in maintaining periodontal tissue homeostasis. However, in periodontitis, pro-inflammatory cytokines, such as interleukin-1beta and tumor necrosis factor-alpha, can promote the destruction of the periodontal tissues (23).

In addition, osteoclasts play a significant role in periodontitis. The inflammatory cytokines released by immune cells and periodontal fibroblasts in periodontitis cause osteoclast activation. Osteoclast activation ultimately leads to the loss of alveolar bone, a defining feature of periodontitis (23). Furthermore, microbial colonization in periodontitis is a crucial part of the disease process in addition to the host response. Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia are a few examples of pathogenic bacteria linked to periodontitis and are thought to contribute to the development and spread of the condition (24). These microorganisms create virulence factors that can undermine host defenses and aid in the survival of the pathogenic biofilm.

Therefore, microbial colonization and host response interact in a complicated way during the pathogenesis of periodontitis. Once bacterial biofilm builds up, immune cells become activated, pro-inflammatory cytokines are produced, and osteoclasts become active, which causes periodontal tissues to be destroyed. To create successful therapeutic approaches to treat periodontitis, it is essential to understand the pathophysiology of the disease and identify the major immune cell types and bacteria involved in the disease process (24).

Although the relationship between the ketogenic diet and periodontitis remains mainly unexplored, understanding the mechanisms of this diet and its impact on other chronic diseases could bring us closer to identifying a correlation. A ketogenic diet exerts various effects on health, including metabolism, brain function, and cancer prevention through ketosis. The pathogenesis of the ketogenic diet involves the production of ketone bodies, which are produced in the absence of carbohydrates. These ketone bodies are metabolized in the liver when the body is in a state of low carbohydrate availability or increased fatty acid breakdown. The body produces small amounts of ketone bodies that can yield 22 ATP each in health (25). This highly efficient process helps the body meet its energy demands when glucose availability is limited. Ketone body production is regulated mainly by insulin, which inhibits ketogenesis when glucose levels are high (26). For this reason, the ketogenic diet has been indicated for diabetic patients—according to a randomized clinical trial, a low-carbohydrate, high-fat diet led to better glycemic control and reduced inflammation (20).

One potential therapeutic effect of the ketogenic diet is a reduction in inflammation. Chronic inflammation is a significant contributor to periodontal disease, and studies have shown that the ketogenic diet does reduce inflammation in the body. This suggests that the diet may have a protective effect on the periodontium. The ketogenic diet has been observed to reduce the expression of various pro-inflammatory markers. These include cyclooxygenase 2, nuclear factor-k, and macrophage inflammatory protein 2. C-reactive protein has been linked to various diseases. Few studies suggest a ketogenic diet may reduce CRP levels, indicating a potential anti-inflammatory effect. A study where a hypocaloric carbohydrate diet was consumed for 12 weeks found that the C-reactive protein levels had significantly lowered (20, 26). A study demonstrated that reducing dietary carbohydrate intake improved pro-inflammatory markers such as TNF-α, IL-6, and IL-8 (27). Another cross-sectional study evaluated the effect of a low carbohydrate diet on two inflammatory markers, IL-1β and Galectin-3. This study further proved that LCD reduced the level of these two inflammatory markers (28).

On the other hand, the ketogenic diet may have adverse effects on periodontal health. It may lead to a decreased production of saliva. Saliva is crucial due to its cleansing effect and neutralizing acids in the mouth. Low salivary production can lead to dry mouth, erosive activity, gum disease, and other oral health problems (19). Additionally, it was found that a high-fat diet can induce periodontitis in mice by increasing the expression of LPS receptors, leading to an inflammatory response (29). It is important to note that this was just a high-fat diet, which shares similarities with the ketogenic diet but differs in various aspects.

Our review identified several studies showing the ketogenic diet's anti-inflammatory effects. This is consistent with a review article published in 2022 by Srivastava et al. This article found that the ketogenic diet has immune-modulatory and anti-inflammatory effects and is therefore beneficial in various chronic inflammatory diseases ranging from polycystic ovary syndrome to cardiovascular diseases and diabetes, and in our case, periodontitis (30). Similarly, our review contained studies that reported reductions in inflammatory markers in individuals following a ketogenic diet, which may contribute to improved periodontal health. Moreover, another review conducted by Pinto et al. (2018) found that the ketogenic diet has antioxidant and anti-inflammatory properties (6). While these studies suggest a possible anti-inflammatory effect of the keto diet on periodontitis, it is essential to note that the current evidence is minimal, and more research is required to fully evaluate the relationship between the ketogenic diet and periodontitis. In addition, many other factors, such as lifestyle and genetics, influence an individual's response to dietary interventions and conditions such as periodontitis. Therefore, while promising results, caution must be taken during interpretation.

Overall, we explored the potential impacts of the ketogenic diet on the periodontium. While several findings suggested a positive anti-inflammatory effect, as discussed above, some articles suggested a negative impact, and some suggested no relationship. Alternatively, Martinon et al. emphasize the importance of nutrient-dense diets containing calcium, polyphenols, and vitamins, which may not necessarily be present in a ketogenic diet (31). Furthermore, they discuss the potential benefits of dietary interventions such as probiotics, prebiotics, and plant-based diets in improving periodontal health (31, 32). Although both reviews emphasize different aspects of diet, both suggest that diet plays a role in the progression of periodontitis. Additionally, both studies recognize the importance of nutrition as a modifiable factor in the advent of periodontal disease.

There are very few interventional studies that directly investigate the nature of the relationship between the ketogenic diet and periodontitis. The current evidence is promising if such a relationship exists due to the ketogenic diet's anti-inflammatory and anti-oxidative effects. However, some studies have reported a potential negative impact of the ketogenic diet due to its high fat content. It cannot be denied that nutrition does play a vital role as a modifiable factor in periodontitis, but the results of specific dietary interventions such as keto remain unknown. More interventional studies with a larger population are needed to come up with a definitive conclusion.

Few limitations exist and must be considered while examining the studies' findings. With the majority of studies describing the effect of keto on other health conditions, there needs to be more scientific research regarding keto and periodontitis. It is also important to note that it is challenging to isolate dietary interventions, making it difficult to establish a correlation. Moreover, more interventional studies need to be conducted. Additionally, there may be individual variations in response to the ketogenic diet, impacting its efficacy in enhancing periodontal health.

Periodontitis has many factors that affect its progression, including lifestyle and nutrition. Growing evidence suggests that nutrition plays a crucial role in periodontitis. However, such a relationship is complex, and the evidence must be sufficient to use dietary interventions as the sole therapeutic approach to periodontitis. The current body of evidence concluded that there may be a relationship between keto and periodontitis, although the evidence is not consistent. It can be implied, however, that it is a positive relationship as the ketogenic diet has been shown to have an anti-inflammatory effect, reducing inflammatory markers found in many diseases, including periodontitis.

With the prevalence of periodontitis and the tremendous therapeutic potential of the ketogenic diet, this relationship cannot be ignored. More evidence is needed to confirm this correlation. Notably, more interventional studies with a larger population are needed to explore the ketogenic diet's effect on the periodontium properly.