Nutrition and Oral Medicine (Nutrition and Health)

174 Part III / Nutrition and Oral Healthwhen mechanisms have been worked out at the cellular laboratory animal level; and (b)even less is known about effects on the oral system.Studies with polyunsaturated fatty acids (PUFA), specifically n-3 PUFA, illustratethe current state of the field (4). Feeding PUFA to animals has resulted in reductions intumor growth and survival; however, high levels of n-3 PUFA (>10% of total fat) fed toanimals or humans can suppress lymphocyte proliferation or activation, natural killercell activity, macrophage activation, and TNF- production. More moderate amountsmay enhance immune functions so that there appears to be a transition between positiveand negative effects that depends on concentration, and probably also on the diseaseload. Dietary n-3 PUFA can lead to changes in cell membrane composition, alterationsin eicosanoid production and signal transduction, and modulations in gene expression(see below). Despite increasing knowledge about the function of n-3 PUFA, it is clearthat more work has to be done to delineate the optimal conditions under which n-3 PUFAcan stimulate the immune response in healthy subjects as well as in patients sufferingfrom various diseases. The same conclusions apply to other macro- and micronutrients.Grimble (22) carried out a meta-analysis of a number of large randomized placebocontrolledtrials using immunonutrition (i.e., supplementation with nutrients known tomodulate inflammatory response to injury and infection) in humans and found improvementsin patient recovery. However, the author was concerned about the difficulty indemonstrating effectiveness of immunonutrition and pointed to uncertainties in antioxidantstatus of subjects as well as genotypic variations. The data suggested that not allgenotypes respond the same way to the nutritional therapy. Clearly, new factors arebeing discovered and all of these must be taken into consideration before meaningfulclinical applications can be developed and tested.3.6. Gene ExpressionThe findings that nutrients can regulate gene expression has brought about a renewedinterest in nutrition and stimulated the interest of researchers in genomics, medicine, andvarious other disciplines but has not yet brought about much interest in oral biology.These approaches and concepts have been applied to studies of diabetes, obesity, cardiovasculardisease, and numerous other health issues. Amino acids, fatty acids, steroids,and trace minerals, among numerous plant and animal products, have been shown toregulate key target genes generally involved in their metabolism (47–50). Clark (51) andJump and Clark (52) showed that PUFAs down-regulate genes that control fatty acidsynthesis and storage, and up-regulate genes that enhance fatty acid oxidation. This shiftin partitioning of fatty acids between storage and catabolism can serve to explain manydietary observations on the beneficial effects of linoleic acid (50). Furthermore, suchmechanisms may play critical roles in obesity and diabetes, two conditions that have beenassociated with periodontal disease. Gene regulation may be one of the common factorsthat play a vital role in all of these conditions. Furthermore, gene polymorphism has beenshown to modulate the response to nutrients (53) and may help to explain the differencesobserved in the responses of different individuals toward nutrient and other therapies.Studies such as these clearly fall into the new field of “nutrigenomics” (54) (Table 1).Within this field, nutrients are seen as “dietary signals that ... influence gene andprotein expression and, subsequently, metabolite production.” High-throughputgenomics, as well as proteomics and metabolomics tools, are used to study the effects of