Nutrition and inflammatory markers
Cyril O. Enwonwu, DSc, PhD, MDS and
Christine S. Ritchie, MD, MSPH
 |
ABSTRACT
|
|---|
Background. Inflammation underlies many chronic diseases. The goal of nutritional support in such diseases is to provide adequate energy and nutrients to meet the increased requirements for synthesis of acute phase proteins, inflammatory mediators, antioxidant defenses and the promotion of tissue repair and restoration of cellular function.
Conclusions. Systemic inflammation alters utilization of various nutrients (fats, carbohydrates and protein) and promotes increased cellular consumption of key antioxidant vitamins and minerals. Some nutrients play a direct role in the resolution of inflammation. These relationships necessitate consideration of the adjunctive role of diet in the natural history of periodontitis.
Clinical Implications. Little is known about the role of nutrition in periodontitis. With rapid advances in molecular biology and nutritional genomics in particular, oral health scientists can address this important area of study.
Key Words: Nutrition; inflammation; periodontal diseaseAbbreviations: APP: Acute phase proteins • APR: Acute phase response • CRP: C-reactive protein • GSH: Reduced glutathione • IL-1: Interleukin-1 • n-3: Omega-3 • PUFAs: Polyunsaturated fatty acids • PD: Periodontal disease • ROS: Reactive oxygen species • TNF-
: Tumor necrosis factor-alpha
Inflammation is an important, protective response by an organism against a hostile challenge (for example, infection, trauma), and it plays a central role in many chronic diseases.1–3 When an organism is exposed to a bacterial challenge, it engages in an orchestrated response to combat the bacteria. This response includes the accumulation of white blood cells (phagocytic leukocytes) in affected tissues and the release of products by these cells that fight the bacteria and recruit leukocytes and inflammatory mediators to the area.2–4 Activated leukocytes release reactive oxygen species (ROS) as part of their attack and promote tissue damage directly or indirectly by stimulating production of proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-).5 Mediators of the local inflammatory changes include nitric oxide and lipid metabolites.1 These responses to external challenges appear to play an important role in the development of chronic disease, especially atherosclerosis.
The inflammatory response may contribute to atherosclerosis by altering blood vessel function, destabilizing atherosclerotic plaques, or exerting inflammatory and thrombotic effects on atherosclerotic plaques.6 There is evidence that genetic variations in some of the proinflammatory cytokines may contribute to the variation in the inflammatory response experienced by a person and his or her subsequent susceptibility to diseases such as periodontitis and coronary artery disease.3
|
INFLAMMATION: A BRIDGE BETWEEN PERIODONTAL AND SYSTEMIC DISEASES
|
|---|
Periodontal diseases (PDs) are among the most common chronic inflammatory conditions seen in adults.4 These chronic infectious processes are exacerbated by risk factors such as diabetes, genetics (particularly IL-1 genotype), malnutrition and smoking.3,7–9 Like in other infectious processes, oral bacteria release normal metabolic products such as fatty acids and lipopolysaccharides, which leads to the production of various inflammatory mediators, including IL-1 and TNF-. Several studies have indicated that severe PDs are associated with a significant increase in serum levels of inflammatory mediators (for example, C-reactive protein [CRP], fibrinogen, haptoglobin, proinflammatory cytokines) compared with control levels.10–13 In these studies, improved oral hygiene reduced the serum levels of inflammatory mediators.10,12 Studies in nonhuman primates have confirmed that even when the bacterial challenge is left intact, periodontal tissue destruction can be reduced markedly by drugs that specifically block the production of proinflammatory cytokines such as IL-1 and TNF-.14
Alterations of diets to more consistently include food high in vitamins and minerals and food rich in omega-3 polyunsaturated fatty acids may have positive effects on periodontal health.
|
THE ROLE OF NUTRITION IN MODULATING INFLAMMATION
|
|---|
The major systemic effect of inflammation or any severe localized inflammation is the acute phase response (APR).15 Proinflammatory cytokines produced in response to local inflammation travel through the blood and stimulate liver cells to synthesize and secrete acute phase proteins (APPs) such as CRP. This APR is at the interface of the interactions between nutrition and immunity in infections.5 Systemic inflammation elicits changes in body composition, alters the use of various macronutrients (that is, fats, carbohydrates and protein) and increases cellular consumption of important vitamins and minerals (that is, micronutrients). Systemic inflammation also promotes the breakdown of protein and fat and loss of muscle mass, and it stimulates the liver to produce more APPs. These changes increase the body’s demand for nutrients from food, particularly in malnourished people.
The APR also promotes production of specific APPs, with increased release of many inflammatory mediators, proliferation of immune cells and several metabolic changes.15 In the process, micronutrients such as vitamin A, iron, copper, selenium and zinc are compartmentalized to the tissues, lost from the body or blocked from cellular use.15 The synthesis of some APPs may be increased by 50 percent in the case of ceruloplasmin and several complement components to as much as 1,000-fold in the case of CRP and serum amyloid A.15,16
Proinflammatory cytokines stimulate APR and promote major changes in protein and amino acid metabolism.9,17 Amino acids released from muscle and other tissues may be inadequate for synthesis of the APPs and essential proteins and, thus, must be supplemented from dietary sources.18 In particular, requirements for specific amino acids such as arginine (a substrate for nitric oxide synthesis), sulfur amino acids, cysteine and methionine may be increased. Tissue repair after an inflammatory process also may increase the requirement for the nonessential amino acid glycine, which is an important component of collagen.8
Increased production of ROS necessitates elevated requirements for the nutrients involved in antioxidant defenses: zinc, copper and selenium. Inflammatory states promote a decrease in the amount of systemic glutathione (reduced glutathione [GSH]) levels. The functions of GSH include antioxidant defense and immune regulation.19 The vitamins pyridoxal phosphate (B6) and riboflavin (B2) are important in maintaining GSH status.20 Selenium has important oxidation-reduction functions, and selenium-dependent GSH enzymes are involved in the reduction of damaging lipid and phospholipid hydroperoxides to harmless products.21
Many other micronutrients—such as beta-carotene and vitamins A, C and E—can become depleted during inflammation.22 The mitochondria contribute significantly to the intracellular burden of ROS, and a study has suggested that dietary vitamin C enters the mitochondria where it protects against oxidative injury.23 In addition to their roles in various immune functions, these vitamins are involved in the maintenance of structural and functional integrity of epithelial tissues and physiological or metabolic parameters relevant to periodontal health.4
Generally, omega-3 (n-3) polyunsaturated fatty acids (PUFAs), which are found in fish such as salmon and in nuts such as walnuts, plus monounsaturated fatty acids, which are found in avocados, olive oil and canola oil, reduce proinflammatory cytokine production.2,24 Adequate dietary intake of n-3 PUFAs increases tissue concentrations of the types of fatty acids (for example, eicosapentaenoic acid and docosahexaenoic acid) that downregulate inflammation.25 Studies suggest that n-3 PUFAs metabolites may serve as "stop signals" for preventing neutrophil-mediated tissue damage.26,27 Studies in animals suggest a positive, modulating effect of n-3 PUFAs on gingival inflammation.28 Studies in humans are limited but have been less promising.29,30
|
NUTRITION AND PERIODONTAL DISEASE
|
|---|
As we noted above, inflammation promotes oxidative stress from ROS, which increases the use of the antioxidant vitamins and minerals. As evidence mounts regarding the relationship between severe PDs and biomarkers of systemic inflammation, dyslipidemia and endothelial dysfunction, it stands to reason that nutrition may serve an important role in both periodontal and systemic inflammation.11,12,30,31 With increasing scientific information on nutritional genomics,32 oral health scientists now have an opportunity to study nutrient-gene interactions and how diet affects the inflammatory mechanisms underlying severe periodontitis.3,6 In a healthy person who is not malnourished, these nutrient needs can be met through a balanced diet. However, alterations of diets to more consistently include food high in vitamins and minerals and food rich in n-3 PUFAs may have positive effects on periodontal health. In addition, oral health clinicians have an important role in advocating healthful diets to their patients, to improve both oral and systemic health.
|
CONCLUSIONS
|
|---|
Systemic inflammation alters the utilization of fats, carbohydrates and protein and accelerates the metabolic consumption of key antioxidant vitamins and minerals. Because of the role key nutrients play in both the modulation of inflammation and the promotion of wound healing, oral health scientists and oral health clinicians would do well to focus more attention on the interface between nutrition and periodontal disease.
|
FOOTNOTES
|
|---|
Dr. Enwonwu is an adjunct professor of biochemistry and molecular biology, School of Medicine, University of Maryland, Baltimore.
Dr. Ritchie is an investigator, Birmingham VA Medical Center, Birmingham, Ala., and a professor of medicine, Division of Gerontology, Geriatrics and palliative Care, Department of Medicine, University of Alabama at Birmingham, 1530 3rd Ave. South, CH-19, Room 219T, Birmingham, Ala. 35294, e-mail "critchie{at}uab.edu". Address reprint requests to Dr. Ritchie.
|
REFERENCES
|
|---|
- Feghali CA, Wright TM. Cytokines in acute and chronic inflammation. Front Biosci 1997;2:d12–26.[Medline]
- Dinarello CA. Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process. Am J Clin Nutr 2006;83(2): 447S–455S.[Abstract/Free Full Text]
- Kornman KS. Interleukin 1 genetics, inflammatory mechanisms, and nutrigenetic opportunities to modulate diseases of aging. Am J Clin Nutr 2006;83(2):475S–483S.[Abstract/Free Full Text]
- Chapple IL. Role of free radicals and antioxidants in the pathogenesis of the inflammatory periodontal diseases. Clin Mol Pathol 1996; 49(5):M247–M255.[Medline]
- Grimble RF. Interaction between nutrients, pro-inflammatory cytokines and inflammation. Clin Sci (Lond) 1996;91(2):121–30.[Medline]
- Makowski L, Hotamisligil GS. Fatty acid binding proteins: the evolutionary crossroads of inflammatory and metabolic responses. J Nutr 2004;134(9):2464S–2468S.[Abstract/Free Full Text]
- Kornman KS, Page RC, Tonetti MS. The host response to the microbial challenge in periodontitis: assembling the players. Periodontol 2000;1997;14:33–53.
- Moore S, Calder KA, Miller NJ, Rice-Evans A. Antioxidant activity of saliva and periodontal disease. Free Radic Res 1994;21(6):417–25.[Medline]
- Phillips RS, Enwonwu CO, Falkler WA. Pro- versus anti-inflammatory cytokine profile in African children with acute oro-facial noma (cancrum oris, noma). Eur Cytokine Netw 2005;16(1):70–7.[Medline]
- D’Aiuto F, Nibali L, Parkar M, Suvan J, Tonetti MS. Short-term effects of intensive periodontal therapy on serum inflammatory markers and cholesterol. J Dent Res 2005;84(3):269–73.[Abstract/Free Full Text]
- Loos BG. Systemic markers of inflammation in periodontitis. J Periodontol 2005;76(11 supplement):2106–15.[Medline]
- Ebersole JL, Cappelli D, Mathys EC, et al. Periodontitis in humans and non-human primates: oral-systemic linkage inducing acute phase proteins. Ann Periodontol 2002;7(1):102–11.[Medline]
- Craig RG, Yip JK, So MK, Boylan RJ, Socransky SS, Haffajee AD. Relationship of destructive periodontal disease to the acute-phase response. J Periodontol 2003;74(7):1007–16.[Medline]
- Assuma R, Oates T, Cochran D, Amar S, Graves DT. IL-1 and TNF antagonist inhibit the inflammatory response and bone loss in experimental periodontitis. J Immunol 1998;160(1):403–9.[Abstract/Free Full Text]
- Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation (published correction appears in N Engl J Med 1999;340[17]:1376). N Engl J Med 1999;340(6):448–54.[Free Full Text]
- Baumann H, Gauldie J. The acute phase response. Immunol Today 1994;15(2):74–80.[Medline]
- Sauerwein RW, Mulder JA, Mulder L, et al. Inflammatory mediators in children with protein-energy malnutrition. Am J Clin Nutr 1997;65(5):1534–9.[Abstract/Free Full Text]
- Moldawer LL. Cytokine regulation of nutrient physiology. In: Nutrition and cytokines: Postgraduate course 10. New York: Aspen; 1992:7–1.
- Sen CK. Nutritional biochemistry of cellular glutathione. Nutr Biochem 1997;8:660–72.
- Grimble RF. Modification of inflammatory aspects of immune function by nutrients. Nutr Res 1998;18:1297–317.
- Rayman MP. The importance of selenium to human health. Lancet 2000;356(9225):233–41.[Medline]
- Semba RD, Tang AM. Micronutrients and the pathogenesis of human immunodeficiency virus infection. Br J Nutr 1999;81(3):181–9.[Medline]
- Sagan KC, Carcamo JM, Golde DW. Vitamin C enters mitochondria via facilitative glucose transporter 1 (Glut1) and confers mitochondrial protection against oxidative injury. FASEB J 2005;19(12): 1657–67.[Abstract/Free Full Text]
- Endres S. Messengers and mediators: interactions among lipids, eicosanoids, and cytokines. Am J Clin Nutr 1993;57(5 supplement): 798S–800S.[Abstract/Free Full Text]
- Ziboh VA. Nutritional modulation of inflammation by polyunsaturated fatty acids/eicosanoids. In: Gershwin ME, German BJ, Keen CL, eds. Nutrition and immunology: Principles and practice. Totowa, N.J.: Humana; 2000:157–67.
- Van Dyke TE, Serhan CN. Resolution of inflammation: a new paradigm for the pathogenesis of periodontal diseases. J Dent Res 2003; 82(2):82–90.[Abstract/Free Full Text]
- Mori TA, Beilin LJ. Omega-3 fatty acids and inflammation. Curr Atheroscler Rep 2004;6(6):461–7.[Medline]
- Vardar S, Buduneli E, Turkoglu O, et al. Therapeutic versus prophylactic plus therapeutic administration of omega-3 fatty acid on endotoxin-induced periodontitis in rats. J Periodontol 2004;75(12):1640–6.[Medline]
- Rosenstein ED, Kushner LJ, Kramer N, Kazandjian G. Pilot study of dietary fatty acid supplementation in the treatment of adult periodontitis. Prostaglandins Leukot Essent Fatty Acids 2003:68(3): 213–8.[Medline]
- Joshipura KJ, Wand HC, Merchant AT, Rimm EB. Periodontal disease and biomarkers related to cardiovascular disease. J Dent Res 2004;83(2):151–5.[Abstract/Free Full Text]
- Seymour GJ, Gemmell E. Cytokines in periodontal disease: where to from here? Acta Odontol Scand 2001;59(3):167–72.[Medline]
- Walker WA, Blackburn G. Symposium introduction: nutrition and gene regulation. J Nutr 2004:134(9):2434S–2436S.[Free Full Text]
TOP
ABSTRACT
INFLAMMATION: A BRIDGE BETWEEN...
