Understanding the relationship between nutrition and gene expression enables one to design an optimal diet based on an individual animal’s genotype.
Proper nutrition plays a key role in maintaining the health and longevity of human and animal populations and their resistance to disease.1-3 In addition to providing an energy source, food and diet directly influence the expression of our genetic potential. In the last 15 years, medical, veterinary and nutritional scientists have begun applying genomics to the field of nutrition. Nutritional genomics (nutrigenomics) is playing an essential role in assuring the quality and safety of human, livestock and pet foods.4-6
In this regard, foods are evaluated for their functional ingredients. Different diets can alter gene expression, resulting in changes in the production of specific proteins and metabolites. Understanding the relationship between nutrition and gene expression enables one to design an optimal diet based on an individual genotype, which can ultimately have a profound effect on the phenotype and observable traits of the person or animal.1-4 Food constituents can act by “up- or down-regulating” target genes, thereby altering their expression. Thus, diets for animals should ideally be tailored to the genome or genomic profile of individuals or breeds in order to optimize physiological homeostasis, disease prevention and treatment, growth, reproduction, and athletic and obedience performances. Nutrigenomics can individualize dietary intervention to prevent, mitigate or cure chronic diseases.1-6
The foundation for achieving individualized nutrition starts by feeding wholesome, fresh and nutrient-dense foods that are selected and optimized based on an individual’s genomic profile.1,5,6
Foods that promote the expression of “healthy” genes are often called “functional superfoods”,1-6 and include certain botanicals, amino acids, vitamins and phytochemicals. All individuals can receive health and longevity benefits from functional superfoods to help prevent or mitigate chronic lifestyle-related diseases, and thus promote a state of optimum health and well-being.2,7,8
Examples of functional superfoods include berries (e.g. blueberries, cranberries), coconut oil, curcumin (turmeric), dark green leafy and yellow orange vegetables, fruits like apples, pears and bananas, medicinal mushrooms, milk thistle, Omega 3 fatty acids, pomegranates, prebiotics (spirulina and soluble and insoluble fiber) and probiotics.
Further, to help pets avoid developing intolerances/sensitivities, rotate foods every one to two months using “novel” animal proteins and gluten-free foods.2 Proteins commonly considered “novel” are bison, buffalo, duck, fish, goat, lamb, pork, turkey and venison. While this approach may seem logical, many people don’t realize that an animal protein source that’s “novel” for one dog or cat won’t necessarily be so for another, unless he has never eaten it before. This is because, unlike a food allergy (which is an immediate reaction), intolerances/sensitivities can build due to prolonged consistent exposure to a particular ingredient. For example, kangaroo, emu and ostrich meats contain proteins that are novel for most dogs in the United States, yet are routinely available in countries like Australia. Similarly, lamb, turkey and venison were once considered novel proteins in the United States but now that they are more mainstream, dogs are beginning to manifest food intolerances/sensitivities to them.1,2
Food intolerances cause a delayed-type immune sensitivity reaction that often begin in the gut, but the antibodies involved are also released in secretions of saliva, tears and sweat, as well as from the nasal passages and ear canals, and the mucosal surfaces of the entire GI and urogenital tracts.1,2 Food intolerance is the third most common condition seen in animals, after flea bite sensitivity and atopy (inhalant allergy). Food intolerance is also the cause of 20% of all allergic skin disease.1
Nutrition, inflammation and oxidative stress
Oxygen is required to produce the high-energy compound ATP coupled to the breakdown of fats, carbohydrates, etc. This process is not 100% efficient, and a lot of O2 is converted to “reactive oxygen species” (ROS), including hydroxyl and superoxide radicals (see Figure 1). ROS quickly react with biomolecules, including lipids, proteins and DNA. Although several protective mechanisms have evolved, an excess of ROS (a condition called oxidative stress) is a primary risk factor for a wide variety of diseases. Oxidative stress, in turn, typically promotes chronic inflammation in which tissues or organs receive inflammatory “mediator” messages that cause them to react as though the “trigger” or pathogen was still present. Rather than repairing themselves, these cells remain in an ongoing state of inflammation that can wax and wane for an entire lifetime.
Antioxidants are now considered vital for inclusion in diets for humans and pets, and are often heavily promoted. Indeed, antioxidants are used in pet foods with higher fat and oil content in an effort to reduce lipid oxidation and the resultant rancid, unhealthy lipid oxidation products.9,10
Many antioxidants in pet foods are oxygen scavengers (see Figure 2) and neutralize ROS in 1:1 reactions. However, some functional foods act at the genomic level, especially via the Nrf2 transcription factor, to stimulate production of antioxidant enzymes. The flavonoids, a large family of polyphenolic compounds synthesized by plants, play a pivotal role in the Nrf2 regulatory pathway of oxidative stress. Dietary flavonoids provide multiple health benefits. In addition to being ROS scavengers, they mainly act as activators of the Nrf2 pathways — stimulating the body’s own defensive systems.
Flavonoids comprise the following subclasses: anthocyanidins (pigmented vegetables and berries), flavanols (tea, berries, apples), flavanones (citrus fruits), flavonols (quercetin; tea, onions, kale, broccoli, apples and berries), flavones (parsley, thyme, celery), and isoflavones (genistein; soybeans, legumes).11,12
Oxidative stress due to reactions of superoxide anion radical, hydrogen peroxide and the hydroxide ion with cellular components is mitigated by the actions of superoxide dismutase and catalase.
Many substances have beneficial antioxidant effects. Several small molecules are ROS scavengers, reacting 1:1 with a single ROS. Hence, large quantities are needed to combat oxidative stress. Other components of the diet, including several carotenoids, activate the expression of Nrf2-regulated genes, increasing the levels of several protective enzymes, including catalase and superoxide dismutase (SOD), with each enzyme capable of inactivating huge numbers of ROS for prolonged periods.
Biomarkers of oxidative stress
Measuring the beneficial or harmful effects of food ingredients in an individual can be accomplished by monitoring certain biomarkers, including levels of ROS scavengers, antioxidant enzymes, and/or byproducts of ROS damage.9-12
Recent human and veterinary research literature has assessed the effects of various factors, including diet, exercise and disease, on the cellular biomarkers of oxidative stress, including antioxidants and chronic inflammation. However, applying this research in practical clinical settings has been hampered by the instability of most relevant biomarkers in blood, tissues and other body fluids. Once the specimens contact air, additional reactions occur that obfuscate the in vivo status of the subject, even if samples are stored frozen at -80°C. Sophisticated laboratory equipment and assays have also been required.
Standard oxidative stress and antioxidant biomarkers9-12 include glutathione (GSH), a measure of Nrf2 (nuclear factor-erythroid-2-related factor 2) activation11,12; total antioxidant capacity (TAC), the sum of low molecular weight scavengers of reactive oxygen species; malondialdehyde (MDA), a by-product of lipid peroxidations, tumor necrosis factor-alpha (TNF-α) a key inflammatory mediator; and antioxidant enzymes including SOD (superoxide dismutase) and catalase. Recent improvements in biomarker assays are allowing their increased use in developing optimized diets for us and our pets.
1Dodds WJ. “Functional foods: the new paradigm based upon nutrigenomics”. J Am Hol Vet Med Assoc 2014; 36: 26-35.
2Dodds WJ, Laverdure DR. Canine Nutrigenomics: The New Science of Feeding Your Dog for Optimum Health. 2015. DogWise Publishing, Wenatchee, WA, pp. 323.
3Essa MM, Memon MA. Food as medicine. New York: Nova Biological, 2013.
4Fekete SG, Brown DL. “Veterinary aspects and perspectives of nutrigenomics: A critical review”. Acta Vet Hung 2007; 55(2): 229-239.
5Kaput J, Rodriguez RL. Nutritional genomics: Discovering the path to personalized nutrition. Somerset, NJ: John Wiley & Sons, 2006.
6Swanson KS, Schook LB, Fahey GC. “Nutritional genomics: Implications for companion animals”. J Nutr 2003;133(10): 3033-3040.
7Laflamme DP. “Nutritional care for aging cats and dogs”. Vet Clin N Am: Sm An Pract 2012; 42(4): 769-791.
8German JB, Roberts MA, Fay L, Watkins SM. “Metabolomics and individual metabolic assessment: the next great challenge for nutrition”. J Nutr, 2002; 132: 2486-2487.
9McMichael M. “Timely topics in nutrition. Oxidative stress, antioxidants, and assessment of oxidative stress in dogs and cats”. J Am Vet Med Assoc. 2007; 231: 714-720.
10Wang J, Schipper HM, Velly AM, et al. “Salivary markers of oxidative stress: a critical review”. Free Rad Biol Med 2015; 85: 95-104.
11Dodds WJ, Callewaert DM. “Novel biomarkers for oxidative stress for veterinary medicine, Parts 1 and 2”. Proceedings AHVMA, Columbus. OH; Sept 2016.
12Kangas K. “A review of oxidative stress and the Nrf2 pathway”. J Am Hol Vet Med Assoc 2016; 44: 8-13.