The Effect of a Fast-mimicking Diet on Periodontal Clinical and Systemic Response to Non-surgical Treatment of Stage III-IV Periodontitis: a Multi-centre Randomised Controlled Trial With Internal Pilot

Introduction

Periodontitis is a microbially-driven inflammatory disease of the periodontium. It has been shown that the periodontitis-associated inflammation is not limited to the periodontium, but may have far-reaching consequences in the rest of the body, and that this may be partly mediated by systemic spread of oral microorganisms. Steps 1 and 2 of periodontal therapy is also associated with a short-term acute phase inflammatory response, characterised by elevation of circulating acute-phase inflammatory markers, which in turn is followed, if successful, by a longer-term reduction in these molecules. In the intermediate to longer term this is accompanied by changes in other markers of peripheral vascular health alongside improvements in metabolic control lasting at least 12 months. Periodontitis is known to have a bidirectional relationship with metabolic disruption and dysregulation. A very recent work corroborated that periodontitis is associated with systemic inflammation as measured by serum C-reactive protein (CRP) levels. Furthermore, it has been reported that intensive non-surgical periodontitis treatment (steps 1 and 2) led to a progressive reduction of CRP after 90 days with a moderate increase at 180 days. It is thought that improvements in metabolic control may also improve periodontal outcomes, yet the exact mechanisms for this are not fully clear. Several human and experimental investigations have also been published concerning the possible effects of nutrition on management of periodontitis. A study on monkeys found that long-term dietary caloric restriction (diet enriched with vitamins and minerals) dampens clinical inflammation and reduces the degree of periodontal breakdown secondary to acute microbial challenge. However, in another experimental study on monkeys, long-term hypocaloric diet (30% less of daily calories intake plus vitamins and minerals) appeared to differentially reduce the production of local inflammatory mediators and the risk for inflammatory periodontal disease among males but not females. In addition, a recent systematic review on animal models concluded that macronutrients that have an effect on oxidative stress or immune system (i.e., n-3 fatty acid) seem to be important for the prevention or treatment of periodontitis. In terms of human research, a Korean group, after a four-week weight control intervention in periodontally healthy obese people, observed a reduction of matrix metalloproteinase (MMP)-8, MMP-9, and interleukin-1β (IL-1β) in gingival crevicular fluid (GCF). A German team reported that a diet consisting of low carbohydrate intake, richness in Omega 3-fatty acids and fibre, higher vitamin C and D values, reduction of animal proteins, and focused intake of nitrate-containing plants might lead to a significant reduction in periodontal and gingival inflammation, even though serological inflammatory parameters and the subgingival microbiome seem to be unaffected. More recently, a study found that there was no overall association between Western dietary patterns (characterized by a higher intake of processed meat, red meat, butter, high-fat dairy products, eggs and refined grains) or prudent dietary patterns (characterized by a higher intake of vegetables, fruit, legumes, whole grains, fish and poultry) and periodontitis; however when solely obese individuals were considered, a Western diet was related to a higher risk of periodontitis. Another very recent investigation, based on use of a dietary inflammatory index, showed that consuming a pro-inflammatory diet was associated with moderate-severe periodontitis in the U.S. general adult population. A novel mode of fasting has been introduced in order to increase patient compliance, due to the fact that people are usually not able to follow a strict diet for a long period. In particular, the fasting mimicking diet (FMD), consisting of 30-50% of the normal caloric intake for 4-7 consecutive days followed by a refeeding ad libitum period once a month, showed very promising beneficious effects in terms of reduction of risk factors for aging, diabetes, autoimmunity, cardiovascular disease, neurodegeneration and cancer. Overall, there is still uncertainty about a potential role of periodic fasting on periodontal clinical and inflammatory parameters. To our knowledge, no studies have investigated the potential effect of FMD on systemic and periodontal response after periodontitis treatment.

Objectives

The main aim of this study is to test if a fasting mimicking diet can influence the systemic and periodontal response following non-surgical periodontal therapy. The null hypothesis is that a fasting mimicking diet does not modify the local and systemic inflammatory post-treatment response.

Study Design