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The identification of inflammatory periodontal disease and education in local and systemic risk factors and their management forms the foundation of the treatment of this disease. Nutrition is potentially a modifiable risk factor that could drive or abrogate the underlying oxidative stress in periodontitis. As research in this area is still in its infancy, clinical guidance on the delivery of dietary advice for susceptible patients is scarce. This paper will explain the possible mechanisms linking nutrition and periodontal disease, as well as the guidelines currently available to the dental profession.
CPD/Clinical Relevance: With a growing evidence base, an appreciation of the links between nutrition and inflammatory periodontal disease can help guide clinicians in educating patients on this potentially important modifiable risk factor.
Article
Periodontitis is an ubiquitous, chronic inflammatory condition affecting 45% of the UK adult population,1 with 11.2% of adults worldwide experiencing severe periodontitis according to the WHO sponsored global burden of diseases study.2 It is initiated by the accumulation of a pathogenic biofilm at and below the gingival margin, which in turn drives a host response which, in susceptible people, is responsible for the substantive tissue damage that arises in periodontitis.
Periodontal health is associated with a ‘health promoting biofilm’, but when the latter is infrequently disrupted/removed by thorough and regular oral hygiene practices it becomes ‘dysbiotic’ and pathogenic species emerge, which drive excess inflammation in those at risk of periodontitis due to such patients possessing a ‘hyper-inflammatory’ immune response. Periodontal therapy has traditionally been directed at reduction of the bacterial load to a level that encourages heath-promoting bacteria, which co-exist symbiotically with a proportionate host response that is in turn associated with resolution of destructive inflammatory cascades. However, to provide long-term stability, it is important that the patient is educated in meticulous home care to maintain the low bacteria load and also address any other underlying risk factors, such as smoking or poorly controlled diabetes.
Risk factors play a huge part in the management of periodontal disease as well as having medico-legal implications if they are not brought to the attention of the patient. There are a variety of risk factors that can both increase biofilm accumulation and also adversely affect the host response in favour of inflammation in susceptible individuals. It is essential that clinicians identify any local (eg calculus, crowding, deep probing pocket depths) and systemic risk factors (eg smoking, stress, diabetes) for disease onset and/or progression and inform patients of them in order to help personalize ways in which to control the inflammatory process. Such counselling and support can be challenging because of the need to engage patients in behaviour change.3
The role of nutrition in periodontitis has recently attracted a surge in research, and its effects on the immune system and inflammatory cascades are well documented. This article will aim to explore the biological mechanisms underpinning nutritional modulation of periodontitis, as well as the clinical guidance that is available to general practitioners.
Nutrition
Nutrition is defined by the World Health Organization as ‘the intake of food, considered in relation to the body’s dietary needs'.4 Diet is simply what an organism eats, but good nutrition involves providing the body with the correct nutrients for that individual's gender, age and levels of physical activity.
Nutrients can be classified into six major classes:
Proteins;
Carbohydrates;
Fats;
Minerals;
Vitamins;
Water.
The first 3 are macronutrients required in large amounts (grams) for energy production, whereas minerals and vitamins are ‘micronutrients’ required in small amounts (milligrams/micrograms) in order to sustain health and wellbeing. Nutritional requirements vary depending upon the population sub-type (eg females/males, adult/children, pregnant, breast-feeding).
Mechanisms linking nutrition and periodontal disease
The pathogenesis of periodontal disease is, in part, driven by oxidative stress. This is defined as an ‘imbalance between oxidants and antioxidants in favour of the oxidants, leading to a disruption of redox signalling and control and/or molecular damage’.5 Indeed, oxidative stress is implicated in a wide range of chronic inflammatory conditions, such as Type 2 diabetes, rheumatoid arthritis and cardiovascular disease. There is also growing evidence suggesting strong associations between periodontitis and these systemic conditions.6,7,8
Oxidative stress can be promoted and also potentially abrogated by certain diets. The ways in which diet can trigger oxidative stress include:
An increase in refined carbohydrates (white breads, sweets, fruit juices) can lead to overloading of the Krebs cycle with excessive production of superoxide radicals as a side-effect of ATP synthesis. These can then produce oxidative stress by overwhelming the antioxidant defence systems within the cell;
An increase in refined carbohydrates and saturated fats leads to neutrophil binding by:
- The formation of advanced glycation end products (AGE) arising due to a chronic hypergylcaemic environment, as glucose binds to proteins in tissues. These then bind to their complimentary receptors (RAGE) on the neutrophil surface and activate various pro-inflammatory signalling pathways (see below).
- The metabolism of excess saturated fats leads to increased production of low density lipoprotein (LDL) cholesterol. This, when oxidized, forms oxidized LDL that binds to toll-like receptor 4 on neutrophils, again activating downstream pro-inflammatory cascades.
Following receptor binding on neutrophils there is also activation of NADPH-oxidase (the respiratory burst) and formation of oxygen radicals ensues.
The formation of oxygen radicals and oxidative stress that follows can lead to activation of redox-sensitive gene transcription factors, such as nuclear factor kappa B (NFkB) and activating protein-1 (AP-1). These are pro-inflammatory gene transcription factors that are activated by an imbalance in the oxidant/anti-oxidant equilibrium and which signal for the production of pro-inflammatory cytokines. These genes are also activated following receptor binding of toll-like receptors and AGE-RAGE interactions.9,10,11
Diets that are therefore high in refined carbohydrates and saturated fats can lead to an inflammatory state via reactive oxygen species (ROS) generation. This effect has been termed ‘meal-induced inflammation’ or ‘post-prandial oxidative stress.’ The incorporation of fibre into the diet helps delay gastric emptying and slows digestion, thus reducing the size of the post-prandial glucose spike, which is associated with inflammatory sequelae.12
Diet can also be implicated in the reduction of oxidative stress. Firstly, a reduction in refined carbohydrates and saturated fats will reduce activation of the pro-inflammatory pathways discussed above. Furthermore, diets rich in antioxidant micronutrients may have a role in reducing oxidative stress. Research has identified, in particular, an antioxidant species called glutathione which, in its reduced form (GSH), is a potent scavenger of oxygen radicals (GSSG being its oxidized form). There is also literature that shows that periodontal disease is associated with depleted glutathione levels and that periodontal therapy has the potential to restore a compromised redox balance by improving GSH levels, although these are not fully restored.13,14 The GSH:GSSG ratio, which governs the ‘redox balance’ of a cell is reduced in peripheral blood neutrophils from periodontitis patients.15 This creates a situation in which the neutrophils are oxidatively stressed and triggers two defence responses:
The antioxidant transcription factor NRF2 (Nuclear erythroid 2 p45-related factor 2) is activated and translocates to the nucleus to stimulate synthesis of more GSH in order to restore the redox balance. This system however appears defective in periodontitis neutrophils and the cells remain stressed.
An enzyme called acid sphingomyelinase is activated and converts sphingomyelin to ceramide that stabilizes the lipid raft structures of the outer cell membrane, where components of the oxygen radical generating NADPH oxidase complex are found.
The result of this is believed to be that when the stressed neutrophils are challenged by bacteria or their products, the oxygen radicals generated are released outside the neutrophil in order to prevent further internal oxidative stress.15
Poly-unsaturated fatty acids (PUFAs) have also been implicated as acting in an anti-inflammatory manner, particularly the omega-3 form (ω-3PUFAs). Ways in which this occur involve:
Down regulation of pro-inflammatory gene expression;10
The production of pro-resolving lipid mediators; resolvins, maresins and protectins. These substances have only recently been discovered and the research evidence behind their application to chronic inflammatory conditions is developing. However, it is clear now that resolution of inflammation is not simply a passive process involving a reduction in pro-inflammatory signals once the stimulus has been removed, but is actually an active response.16,17
One small study in particular has demonstrated the potential for diet in regulating inflammation. It demonstrated that individuals placed on a ‘stone-age’ diet for 4 weeks, that is, low in refined carbohydrates and high in antioxidant micronutrients and fibre, demonstrated a reduction in gingival bleeding and probing depth, despite the presence of increased plaque scores as a result of no access to toothbrushing methods. Table 1 summarizes the various micronutrients that have a potential association with periodontal inflammation.18
A powerful and essential antioxidant required from diet.
On oxidation forms dehydroascorbic acid (DHAA) which can be converted back to ascorbic acid endogenously by GSH. Maintaining sufficient Vitamin C levels via diet can therefore preserve GSH levels within the cell.
A co-factor for enzymes (eg lysyl hydroxylase) involved in collagen synthesis. Vitamin C therefore promotes collagen synthesis and there is evidence of down-regulation of these enzymes in the presence of periodontal pathogens.19
Smoking will reduce serum Vitamin C and GSH levels.9
Vitamin C may be useful in enhancing chemotaxis of neutrophils (PMNLs) in both healthy individuals and also those with Chediak-Higashi Syndrome where the association of periodontal destruction is well established.9 Impaired PMNL chemotaxis is a recognized feature of periodontitis.20
Vitamin C deficit is associated with necrotizing ulcerative gingivitis.
Vitamin D and Calcium
Vitamin D
Milk
Salmon
Tuna
Beef/Chicken Liver
Egg yolk
Calcium
Milk/milk products
Spinach
Tofu
Vitamin D and calcium are essential for maintaining bone mass.
Vitamin D has recently been implicated in the immune response with Vitamin D receptor (VDR) stimulation resulting in the formation of its biologically active component (1,25(OH)2D3). This can then stimulate the production of antimicrobial peptides that could be important in host defence.9
The role of Vitamin D and calcium in periodontal health is unclear. Some studies show an association between bone loss and osteoporosis as well as potential polymorphisms in the VDR gene in periodontitis subjects.21,22 There is a need for further randomized controlled trials in this area.
Magnesium
LentilsTofuPeanutsBean sproutsSpinach
Higher Mg/Ca ratios have been associated with reduced levels of periodontitis within populations.23
Magnesium is implicated in the inhibition of free-radical generation and hypomagnesemia can lead to activation of PMNLs. This may provide a link between magnesium deficiency and a heightened inflammatory response.23
Further research is required to determine the role of magnesium in periodontitis more clearly.
Clinical guidelines
This article has mainly summarized the early research and molecular physiology underpinning the associations between diet and periodontitis. However, the principal goal for research is to translate findings into superior patient care and for it to be relevant it must have a place in clinical dentistry.
It is recognized that much of the research to date has not yet led to human intervention studies and also demonstrates variations in the assessment methods employed for nutritional status. The use of self-reporting questionnaires may not be ideal, particularly in terms of patient compliance with nutritional interventions, although more modern methods of determining nutritional status, such as measuring serum micronutrient levels, will help to address this to some degree.
Whilst the current evidence base demonstrating the direct effect of nutrition and periodontal inflammation is limited, it is worthwhile mentioning that diet also interacts with other risk factors associated with periodontal disease. For example, in the case of un-/poorly controlled Type 2 diabetes, diets low in refined carbohydrates help to avoid a chronic hyperglycaemic state, which predisposes to excessive inflammation and therefore likely impacts upon the course of periodontitis.
It is important to note that single vitamin/antioxidant supplementation is unlikely to provide best benefit as vitamin radicals form following radical scavenging and may be as damaging as the oxygen radicals they remove from the cells and tissues. This may arise, for example, in patients who are nutritionally replete but who continue to take mono-vitamin supplements and who may thus overload on such supplements.9,11
Nutritional interventions also impact upon individuals differently, due to genetically-based differences (‘nutrigenetics’), an emerging area of research. This may therefore result in no single best protocol or ‘one size fits all’ approach to the control of periodontal inflammation by nutrition, pointing towards a tailored approach to individual patients.9
The Seventh European Workshop on Periodontology acknowledged that robust evidence for managing periodontal disease with dietary recommendations is lacking. However, dietary recommendations are provided based on the current literature and are highlighted in Table 2.24 These recommendations are essentially the same as those provided to the dental professional in the Department of Health document Delivering Better Oral Health: An Evidence-Based Toolkit for Prevention, although this document provides more advice as part of a general health message (Table 3).25
Dietary Recommendations for Prevention/Treatment of Periodontal Inflammation
■ Increase dietary intake of fibre, fish oils, fruit, vegetables and berries
■ Reduce intake of refined sugars
■ In obese patients advise restriction of caloric intake
Healthier Eating Advice
Base meals on starchy foods
■ Eat lots of fruit and vegetables
■ Eat more fish
■ Cut down on saturated fats
■ Eat less salt (no more than 6 g daily)
■ Cut down on amount and frequency of sugary food (added sugar should be less than 10% of total energy in diet and ideally less than 5%)
Providing dietary advice also falls in line with the current European Federation of Periodontology manifesto and strategic plan and the vision of the British Society of Periodontology (BSP) of ‘Periodontal health for a better life’, that calls upon the entire dental team to engage in the prevention, early diagnosis and treatment of periodontal disease as part of improving general health.26,27
Conclusion
Research into nutritional risk factors and modulators of periodontal inflammation is in its infancy, but holds promise for targeted prevention and treatment approaches in patients with specific nutritional depletion or those with nutrigenetic factors that impact negatively on their ability to absorb or metabolize key dietary nutrients. Nutritional interventions aimed at a ‘one size fits all’ therapeutic approach may be limited in their efficacy but considerably more research is required before the impact of specific nutritional deficiencies upon periodontitis risk and progression is fully understood. Until then, a pragmatic approach seems indicated whereby all dental professionals should inform susceptible patients of the potential benefits of diet on the periodontium, particularly in conjunction with other risk factors, and advise on healthy eating.
Declaration of Interests
This article was written as part of an audit funded by the British Society of Periodontology entitled, ‘ Explaining diet as a risk factor for periodontal disease in primary dental care’.
