A Summary Of The Lecture Given By The Keynote Speaker, Professor Iain Chapple, At The BVDA Scientific Meeting 30 March 2011
Periodontal disease increases the rates of all cause mortality in humans. Why? It is believed to be due to the inflammatory process associated with periodontal disease. Elevated levels of biomarkers of inflammation are found in the bloodstreams of patients who have periodontitis over those who do not have the disease.
The majority of chronic disease is explained by major modifiable risk factors, namely poor nutrition, physical inactivity, smoking and possibly periodontitis. The Cumulative Risk Factor Model shows the impact of focal inflammation on common risk; co-morbidity factors such as rheumatoid arthritis, cardiovascular disease, obesity, type 2 diabetes, smoking pathologies and periodontitis act together to increase the risk of atherosclerosis. Patients with a pro-inflammatory phenotype have been shown to be more prone to chronic low grade periodontal inflammation than normal, which could, if present over many years, result in increased mortality from cardiovascular disease. It has been shown that increased periodontal inflammation results in increased risk of atherosclerosis. Equally, reducing the inflammation reduces the biomarkers of
Biofilm Bacteria Or Pro-Inflammatory Mediators?
Teeth are coated by a biofilm which can be a health promoting biofilm, but if allowed to accumulate and mature, becomes predominantly gram negative and pathogenic. There is always a microbial challenge in the mouth, especially of animals, which is controlled by the host immuno-inflammatory response. It is the pro-inflammatory mediators, like cytokines and prostaglandins produced during this inflammation, which result in periodontal bone loss, spill into the circulation and can increase risk of cardiovascular disease; not necessarily the actual bacteria themselves.
It has been accepted for many years that the presence of plaque is a prerequisite and risk factor for gingivitis. If the body’s immuno-inflammatory response to the oral microbial challenge is balanced, the antibodies and polymorphonucleocytes (PMNs) repel the microbes, resulting in a non-progressive gingivitis. This can deteriorate to periodontitis when an unbalanced host response results in the release of cytokines, prostanoids, matrix metallo-proteinases and reactive oxygen species, all of which interfere with connective tissue and bone metabolism resulting in a progressive periodontitis. Controversially, in 1977, Hillam and Hull published research suggesting that patients with gingivitis also accumulated more plaque.
There are several factors which contribute to the hyper-inflammatory response in periodontitis, manifest by elevated inflammatory mediators in tissues and/or blood, despite clinical health. These include genetic exposures, e.g. genetic polymorphisms; environmental exposures, e.g. bacterial infection, stress (neuroendocrine pathways); drug exposures e.g. non-steroidal anti-inflammatory drugs and corticosteroids; and behavioural exposures, e.g. exercise, diet and nutrition. These four exposures interact with each other to differing degrees in different individuals and have a combined effect on the body’s inflammatory status that varies from one patient to the next.
Most importantly, studies have shown that gene expression is directly affected by the environment immediately surrounding the genes. Good nutrients surrounding the genes will enhance the expression of healthy genes and suppress the expression of deleterious genes. This is so important because it has an impact on overall health and longevity.
Refined Sugars And Inflammation
What we eat actually drives inflammation, as well as affecting gene expression. Research has shown that the presence of excess glucose in the blood triggers inflammation, including gingivitis. In a single blind cross-over study, Sidi and Ashley gave sugar (boiled sweets) to the test subjects 9 times per day between meals for 3 weeks. Compared with the control leg of the study, there was no difference in plaque scores for high or low sugar diets, but the high sugar diet resulted in significantly more gingival inflammation and bleeding. Why?
Pro-Inflammatory And Anti-Inflammatory Nutrients
The impact of nutrition on inflammation is a balance between pro-inflammatory and anti-inflammatory nutrients. Refined carbohydrates, saturated fats (dairy products, animal fats, some oils (coconut oil and palm kernel oil) and saturated fatty acids) are pro-inflammatory nutrients. On the other hand, polyunsaturated fatty acids (PUFAs) and antioxidants (e.g. carotenoids from green vegetables, tomatoes, fruits; polyphenols from vegetables, red wine, tea, pomegranates; vitamins from fruits, vegetables and sunlight) are known to be anti-inflammatory.
During the production of energy by the cells, free radicals (FR) are produced as inevitable, but detrimental, by-products. A free radical could be defined as any species capable of independent existence (hence the term “free”) that contains one or more unpaired electrons. This most commonly affects oxygen, producing reactive oxygen species (ROS). Free radicals aggressively search for an electron to form a pair with the lone electron, so balancing their outer shell. Antioxidants supply this missing electron to the free radical, preventing it from causing cellular damage. If there are insufficient antioxidants or excessive free radicals, the search for an electron to quench the free radical becomes damaging. The easiest place for the FR to steal an electron from is fat, and the most readily available source of fat is the phospholipid bi-layer of all cell and organelle membranes. So free radicals cause immense damage to cell membranes, organelles and even DNA. It has been estimated that every cell in our body is attacked by free radicals 10,000 times per day.
Mitochondria are responsible for nearly all energy production in the body via the Krebs cycle, which takes place in the christae within the mitochondria. Excessive sugar and saturated fat drive the Krebs cycle too fast, producing vast numbers of free radicals, which spill out of the mitochondria into the cellular cytoplasm. The most potent cellular antioxidant, glutathione, neutralizes as many of these free radicals as possible, but is quickly overwhelmed, allowing free radicals to attack other organelles (including the nucleus and DNA) within the cell. Free radicals also leak out of the cell and damage its neighbours, resulting in the tissue damage and inflammation which underlies all disease.
Conditions of excessive dietary refined carbohydrates, sugars and saturated fats are likely to be accompanied by deficient dietary intake of antioxidants and the anti-inflammatory omega 3 unsaturated fatty acids. The resultant overproduction of free radicals in an environment deficient in antioxidants allows the free radicals to cause enormous damage, known as oxidative stress. Prof. Dr. Helmut Sies (1986) stated: “Oxidative stress is defined as a process in which the balance between oxidants and antioxidants is shifted towards the oxidant side. This shift can lead to antioxidant depletion and potentially to biological damage if the body has insufficient reserve to compensate for consumed antioxidants.” Oxidative stress is the key orchestration point for the diverse signalling pathways that control inflammation.
Glutathione Controls Inflammation
It is essential to remember that when the antioxidant has donated an electron to the free radical, it itself is damaged and needs to be repaired in one of the many antioxidant regeneration cascades. In fact, research has shown that taking an antioxidant in isolation is more harmful than taking a placebo, so all vitamins and antioxidants are best taken in the form of whole foods, not man-made isolates. The intracellular antioxidant, glutathione, controls redox-regulated inflammatory genes as well as being a potent antioxidant in its own right. In this way, glutathione controls inflammation.
Free Radical Damage
In removing electrons from molecules, free radicals cause folding of proteins, shortening of telomeres (cellular senescence), random gene activation and damage to unsaturated fatty acids, nucleic acids, small organic molecules (e.g. vitamins and glutathione) and much more.
Those very same factors that were earlier shown to result in hyper-inflammation have now been shown to be equally involved in oxidative stress and antioxidant depletion, namely rheumatoid arthritis (dePablo et al 2008), obesity (Pischon et al 2007), type 2 diabetes (Taylor et al 2008), smoking related pathologies (Palmer et al 2005), cardiovascular disease (Dietrich et al 2008) and periodontitis (Chapple et al 2002). The pathways for both are undoubtedly interdependent.
The Neutrophil Extracellular Trap
More exciting research has just been completed involving the exacerbation of inflammation by the neutrophils (Palmer L et al, 2011, in press). Neutrophils are attracted to sites of inflammation as part of the immune response. When they die, their DNA is released, studded with lysozymes, forming a net. This biologically dangerously active neutrophil extracellular trap (NET) aids the immune response but is also implicated in auto-immune diseases like rheumatoid arthritis, systemic lupus erythematosus and small vessel vasculitis. Periodontitis aggravates this neutrophil hyperactivity, which continues at a low level in susceptible patients, even after the thorough removal of plaque.
The Cause Of Periodontitis
So, does periodontitis cause the far reaching inflammation? Or is periodontitis one of the more visible signs of inflammation affecting many parts of the body simultaneously, with clearly differing clinical pictures, caused by some other underlying risk factors?
A diet rich in refined carbohydrates and excess saturated fats increases free radical production (oxidative stress) resulting in systemic inflammation (Monnier et al 2006). “Meal-induced inflammation” is now the term applied to post-prandial oxidative stress.
Consuming refined carbohydrates causes sudden increases in serum glucose levels, known as “glucose spikes”. These are thought to promote inflammation.
How Can We Eliminate “Glucose Spikes” And Resultant Inflammation?
As humans, by changing our dietary habits to include more raw fruits, vegetables, nuts and seeds, unsaturated fatty acids and fibre.
For rabbits, this means a diet of grass and hay.
For dogs and cats, a diet of raw meat and raw bone with liquidized raw green vegetables will prevent the glucose spikes and the ensuing inflammation.
Two supplements are available which have been researched and may do the same thing. These are Juice Plus for humans (Chapple ILC, 2011) and Pet Plus for pets (Penman and Tuck, 2000).
Processed pet foods are full of refined carbohydrates, saturated fats and denatured proteins. Is it any wonder we are confronted with such an alarming array of diseases in our pets these days?
Remember, refined carbohydrates cause oxidative stress and inflammation, the cause of all disease processes. Juice Plus and Pet Plus provide numerous antioxidants, phytonutrients, vitamins, minerals and other essential micronutrients which help to prevent oxidative stress and inflammation, thus reducing the risk of disease in a simple way.
1. Sidi and Ashley (1983)
Journal of Periodontology 55: 419-423
2. Sies H (1986) Biochemistry of Oxidative Stress.
Angewandte Chemie International Edition 1986: 25
3. Chapple ILC et al (2002)
Journal of Clinical Pathology: Molecular Pathology 55:367-373
4. Palmer L, Cooper PR, Chapple ILC (2011)
Hypochlorous acid (HOCl) regulates neutrophil extracellular trap (NET) release.
Journal of the Federation of American Societies for Experimental Biology April 2011 25
(Meeting Abstract Supplement) 116.7 (in press) .
5. Monnier L, Mas E, Ginet E, et al (2006)
Activation of oxidative stress by acute glucose fluctuations
compared with sustained chronic hyperglycemia in patients
with type 2 diabetes.
Journal of the American Medical Association 295:1681-1687
6. Chapple ILC et al (2011)(in press)
Impact of dietary augmentation with dried whole fruit,
vegetable and berry juice concentrates upon outcomes of
periodontal therapy: a randomized controlled trial.
7. Penman and Tuck (2000) A pilot study to explore the
effects of active enzymes on the oral health of cats and dogs.
BVDA Journal 2000