On the surface, it appears that Type 2 diabetes is genetic and hereditary because multiple family members acquire the disease. This creates a sense of hopelessness and people "give in" to the disease because it appears to be genetic and there's nothing that you can do if it's genetic.

But, it turns out that our Nutrition impacts how Genes function at the cellular level and how this interaction affects health. This is an important topic because of how diet affects the way genes are expressed, the effect of genes on how the body uses nutrients, and the effects of nutrients on molecular level processes in the body.

The regulation of Gene Expression gives the cell control over the versatility and adaptability of any organism and serves as a substrate for evolutionary change. This is profound since our diet has some impact on our genetic code which is passed on to the next generation. The more nutritious our diet the stronger will be the genes which will get passed on. We are what we eat. But to some extent, our children and grandchildren are what we eat also.

Let’s step back briefly to some basic biology. A Gene is the basic unit of heredity in all organisms. All living things depend on DNA to pass on their traits to offspring. In cells, a gene is a portion of an organism's DNA which contains both "coding" sequences that determine what the gene does, and "non-coding" sequences that determine when the gene is active (expressed.)

When a gene is active, the coding and non-coding sequences are copied producing an RNA copy of the gene's information. RNA is central to protein synthesis. This piece of RNA can then direct the synthesis of proteins via the genetic code. Gene expression is the process by which inheritable information stored in a gene is made into functional gene products such as protein or RNA.

From a practical standpoint, knowledge of the interactions between Gene Expression and Nutrition can be applied in the field of nutrigenetics to improve dietary guidelines for populations, or to tailor-make specific diets for individuals.

The interaction between diet – health – genes can aid tailor-made specific diets for individuals for preventative health management and as an aid in curing illness.

This interaction can also be utilized by athletes to maximize athletic performance. Lance Armstrong is probably as good a scientist on self nutrigenetics and athletic performance as he is a cyclist. His detailed focus on his nutrient intake played a key role in his cycling success.

Interaction between Gene Expression, Nutrition and Metabolism
There currently is great interest and research in understanding the interaction between nutrition - health – genes as it impacts metabolism. There is recognition that increasing knowledge on metabolic pathways to gain understanding on metabolism as a whole, will help provide guidance to individuals to make specific changes to their diets and lifestyles to affect metabolism in a net positive direction.

What scientists learn about the interaction between Gene Expression and Nutrition will have the potential to help prevent many diseases, and greatly affect our optimal nutrition and health. As we each differ in our metabolic regulation, the optimal diet for one person is not necessarily the optimal one for another -- but, it turns out that there are key attributes of a healthy diet for most people, i.e. plant-based foods, whole foods, unprocessed foods, etc.

Eating natural foods and eating only the amount of calories our bodies need to be strong and fit is part of a greater lifestyle choice and philosophy.

A healthier lifestyle philosophy is to live prudently and efficiently, consuming only what we need. Many of our modern lifestyle diseases, such obesity, hypertension and heart disease are the result of eating heavily processed foods, more calories than our bodies need and consuming excess salt and trans fats and hydrogenated oils. Our food habits also impact our resting heart rate - an important health indicator. 

Numerous studies (with yeast and mammals) clearly indicated that longevity is significantly enhanced with a calorie restrictive diet. In these studies it is possible this enhanced life span is in part due to adaptation ability that maximizes utilization of the lower calories creating some metabolic efficiency. These studies also support the conclusion that the quality of the restricted calories can be as important a factor as portion control.

There is a relatively new theory that low-calorie diets activate genes designed to help animals endure hard times, which boost cellular repair mechanisms. There is evidence that almost all animals, including humans, may have a similar suite of genes.

The challenge for each of us is to find the right mix of calorie count with the best calorie quality to reach our optimum body weight that sustains a high but efficient metabolism.

Calorie intake needs to support and maintain a high metabolism that supports an active lifestyle and routine that includes vigorous exercise. Portion control should not sacrifice a high metabolism as the objective is not to live a longer but weaker and restrictive life, but to instead lead a longer, stronger and more vital life. Olympic swimmer Michael Phelps consumes 10,000 calories to support his ideal metabolism needs.

The quality of our calories is very important. A high quality nutritious diet  (such as the Death to Diabetes Nutritional Model) helps us achieve metabolic efficiency. The highest nutritional food is that which is produced naturally and organically.

Vegetables, fruits and some organic whole grains are packed with nutrients. Processed food is devitalized of essential vitamins, minerals and energy and is filled with empty calories. Natural food has been produced capturing the energy of the sun.

In many instances, organically grown food has a higher nutrition content than artificially fertilized mass produced foods.

As most European farms are smaller than the large American farms, European farmers are able to build and maintain rich soils by fertilizing their land with manure (mostly cow) instead of artificial and incomplete fertilizers used by large American farmers. Rich soils produce a higher crop yield with a higher nutrient content. American organic farming attempts to follow the European experience.

Natural Sources of Essential Nutrients

Here is a list of key nutrients and their natural food sources. (Sources: National Institute of Health and Linus Pauling Institute at Oregon State University)

Macronutrients

Protein: Protein is an essential nutrient that is needed on a daily basis. Proteins are made up of ‘essential’ and ‘non-essential’ amino acids. Essential amino acids are not able to be produced by the body, but instead are obtained only by eating high quality protein. Protein sources that contain all the essential amino acids are considered Complete Proteins.

Sources: Meat, poultry, fish milk, whey protein, whole eggs, yoghurt, cheese, cottage cheese, whole wheat bread, grains, quinoa, buckwheat, pasta. Non-essential amino acids are produced by the body.

Sources: Asparagus, broccoli, peanuts, soy (for women only), cauliflower, beans, walnuts, potato, cantaloupe, avocado, strawberry, orange, banana, peaches, blueberry. Amino acids are composed of nitrogen, carbon, oxygen, and hydrogen molecules. Proteins are essential to (i) repair body cells, (ii) build and repair bones and muscles, (iii) provide an energy source, and (iv) control essential metabolic body processes.

Carbohydrates: Athletes know that carbohydrates (sugars and starches) play an important role for energy and performance. Carbohydrates are also the brain’s most important fuel source. Carbohydrates in the form of glycogen are stored in the muscles to fuel physical activity and in the liver to fuel brain and other cells. Carbohydrates in the form of glucose reside in the blood stream and play a controlling signal for metabolic regulation.

In nature, plant photosynthesis converts the sun’s light energy into carbohydrates and oxygen. That is why carbohydrates from whole grains, vegetables and fruits are excellent carbohydrate sources to be preferred over processes food sources. Carbohydrates prevent fatigue.

Sources: Whole grains such as oats, amaranth, quinoa, rice, barley; milk, yogurt, cottage cheese, vegetables, (especially, green, leafy vegetables, potatoes, sweet potatoes, carrots, beans and peas) and fruits (especially, dates, raisins, banana, grapes, pears, plums, blackberries, blueberries and apples).

Fats: Unfortunately, many diets focus on "low fat", "no fat" or "low cholesterol", creating this false belief that all fat is bad. Ironically, these low-fat diets led to high-carb or high-protein diets that created today's epidemic of diabetes, obesity, and heart disease!  Good fats include monounsaturated fat, Omega-3 polyunsaturated fat, and some Omega-6 polyunsaturated fat.

Sources: Monounsaturated fat is contained in extra virgin olive oil, macadamia nuts, cashews, avocados, peanuts, walnuts, and almonds. Other foods/oils such as hazelnuts, Brazil nuts, sesame seeds, pumpkin seeds, pecans, and rice bran oil contain monounsaturated fat but have higher levels of saturated and polyunsaturated fats. Monounsaturated fat, which is considered to be the healthiest fat, contains large amounts of monounsaturated fatty acids (MUFAs), which are predominantly found in olive oil (73%) and macadamia nut oil (80%). Oils high in monounsaturates are better oils for cooking, although extra virgin coconut oil is even better under the heat.

Omega-3 polyunsaturated fat is another healthy fat that is contained in flaxseed oil, hemp oil, pumpkin seeds, walnuts and oily fish, such as wild salmon, sardines, tuna, mackerel, trout and herring. Plant-based foods such as flaxseed, nuts, and wheat germ contain one of the Omega-3 EFAs, alpha-linolenic acid (ALA). Marine crustaceans and oily fish such as wild salmon, tuna, sardines and mackerel contains the other two common Omega-3 EFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Other sources of Omega-3 EFAs include dark green vegetables such as seaweed, broccoli, spinach, kale; and, other green vegetables like spring greens, dark salad leaves, cabbage, Brussels sprouts, and parsley. Walnuts are the only nut that contains both monounsaturated fat and Omega-3 EFA.

Omega-6 polyunsaturated fat is contained in walnuts, sesame seeds, sunflower seeds, black currant seed oil, evening primrose oil and borage oil, which contain the Omega-6 EFAs, linoleic acid (LA) and gamma-linolenic acid (GLA) Use GLA to activate Omega-3 fatty-acids (via delta-6 saturase), ensuring absorption by the plasma cell membrane while inhibiting delta-5 desaturase (conversion to arachidonic acid).

Micronutrients

Calcium: Calcium is the most abundant mineral in the human body, has several important functions. Calcium is needed to build bones and teeth and for muscle contraction, blood vessel contraction and expansion, the secretion of hormones and enzymes, and sending messages through the nervous system. A constant level of calcium is maintained in body fluid and tissues so that these vital body processes function efficiently. Sources: Yogurt, sardines, cheese, milk, salmon, cottage cheese, spinach, kale, broccoli, whole wheat bread.

Vitamin D:   Vitamin D is a fat-soluble vitamin that is naturally present in very
few foods.  It is also produced when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis.  Vitamin D is essential for promoting calcium absorption in the gut and enables normal mineralization of bone.  Vitamin D has other roles in human health, including modulation of neuromuscular and immune function and reduction of inflammation. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D.  Sources: The Sun, cod liver oil, salmon, mackerel, tuna, sardines, milk, eggs, liver, and cheese.

Vitamin B12: Vitamin B12 maintains healthy nerve cells and red blood cells, helps make DNA.  Sources: Mollusks, clams, liver, beef, yogurt, milk, eggs, chicken.

Vitamin B6: Vitamin B6 performs a wide variety of functions in your body and is essential for your good health. For example, vitamin B6 is needed for more than 100 enzymes involved in protein metabolism. It is also essential for red blood cell metabolism. The nervous and immune systems need vitamin B6 to function efficiently. Hemoglobin within red blood cells carries oxygen to tissues. Your body needs vitamin B6 to make hemoglobin. Vitamin B6 also helps increase the amount of oxygen carried by hemoglobin. Vitamin B6, through its involvement in protein metabolism and cellular growth, is important to the immune system. It helps maintain the health of lymphoid organs (thymus, spleen, and lymph nodes) that make your white blood cells. Vitamin B6 also helps maintain your blood glucose (sugar) within a normal range. Sources: Potato, banana, garbanzo beans, chicken, oatmeal, beef spinach, salmon, wheat bran, peanut butter.

Thiamin: Thiamin, also called Vitamin B1, is important in glucose metabolism and the conversion of food into energy.   Thiamin requirements increase with strenuous physical exertion, fever, pregnancy, breast-feeding, and adolescent growth. Sources: Wheat germ, pasta, peas, rice, lentils, milk, whole wheat bread, nuts, pecan, spinach, cantaloupe, rice and eggs. 

Riboflavin: Riboflavin enzymes are critical for the metabolism of carbohydrates, fats, and protein and are part of the electron transport (respiratory) chain, which is central to energy production. Riboflavin is is involved in the metabolism of several other vitamins (vitamin B6, niacin, and folic acid)., factors. Riboflavin deficiency alters iron metabolism. Research suggests that riboflavin deficiency may impair iron absorption, increase intestinal loss of iron, and/or impair iron utilization for the synthesis of hemoglobin. Improving riboflavin nutritional status has been found to increase circulating hemoglobin levels.  Sources: Milk, eggs, pasta, almonds, spinach, beef, asparagus, broccoli, salmon, cheese, chicken, and whole wheat bread.

Pantothenic Acid: Pantothenic acid, also known as vitamin B5, is essential to all forms of life. Pantothenic acid is found throughout living cells in the form of coenzyme A (CoA). CoA is required for chemical reactions that generate energy from fat, carbohydrates, and proteins. The synthesis of essential fats, cholesterol, and steroid hormones requires CoA, as does the synthesis of the neurotransmitter, acetylcholine, and the hormone, melatonin. Heme, a component of hemoglobin, requires a CoA-containing compound for its synthesis.  Sources: Avocado, yogurt, sweet potato, chicken, milk, lentils, eggs, broccoli, peas, whole wheat bread and tuna.

Biotin: Biotin, a Vitamin B complex, plays a role in DNA replication and transcription, cellular proliferation, amino acid metabolism fats.  Sources:  Liver, eggs, yeast, wheat bran, whole wheat bread, cheese, avocado, salmon, chicken, cauliflower, raspberries, avocado.

Niacin:  Niacin is also known as nicotinic acid or vitamin B3. Nicotinamide is the derivative of niacin and used by the body to form the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP).  Living organisms derive most of their energy from oxidation-reduction reactions, which are processes involving the transfer of electrons. As many as 200 enzymes require NAD and NADP, mainly to accept or donate electrons for redox reactions. NAD functions most often in energy producing reactions involving the degradation (catabolism) of carbohydrates, fats, and proteins. NADP functions more often in biosynthetic (anabolic) reactions, such as in the synthesis of all macromo fatty acids and cholesterol.  NAD also plays a role in cell signaling, DNA repair and use of calcium.  Sources: Chicken, turkey, beef, salmon, whole wheat bread, yeast, pasta, peanuts, lentils, and lima beans.

Folate: Folate helps produce and maintain new cells, especially important during periods of rapid cell division and growth such as infancy and pregnancy. Folate is needed to make DNA and RNA, the building blocks of cells. It also helps prevent changes to DNA that may lead to cancer. Folate is needed to make normal red blood cells and prevent anemia. Folate is also essential for the metabolism of homocysteine, and helps maintain normal levels of this amino acid. Sources: Beef, liver, peas, pasta, spinach, asparagus, rice, broccoli, egg noodles, avocado, peanuts, wheat germ, tomato juice, orange juice, whole wheat bread, eggs, cantaloupe, papaya, and banana.

Iron:  Iron is essential to normal human physiology, and is an integral part of many proteins and enzymes that maintain good health.  Iron is an essential component of proteins involved in oxygen transport. It is also essential for the regulation of cell growth and differentiation. A deficiency of iron limits oxygen delivery to cells, resulting in fatigue, poor work performance, and decreased immunity. Sources: Chicken livers, oysters, beef, Turkey, chicken, halibut, tuna, shrimp, pasta, oatmeal, soybeans, lentils, beans, molasses, spinach, peas, grits, raisins, whole wheat bread.

Potassium:  Potassium is an essential dietary mineral and electrolyte (a substance that dissociates into ions (charged particles) in solution, making it capable of conducting electricity. Potassium is the principal positively charged ion in the fluid inside of cells, while sodium is the principal ion in the fluid outside of cells. A cell's membrane potential is maintained by ion pumps in the cell membrane, especially the sodium, potassium-ATPase pumps.

These pumps use ATP (energy) to pump sodium out of the cell in exchange for potassium. Their activity has been estimated to account for 20%-40% of the resting energy expenditure in a typical adult. The large proportion of energy dedicated to maintaining sodium/potassium concentration gradients emphasizes the importance of this function in sustaining life. Tight control of cell membrane potential is critical for nerve impulse transmission, muscle contraction, and heart function. Sources: The richest source of Potassium is fruits and vegetables: banana, potato, prune juice, plums, orange, tomato, artichoke, lima beans, acorn squash, spinach, sunflower seeds, almonds, and molasses. Milk is also an excellent source of Potassium.

Vitamin E: Vitamin E acts to protect your cells against the effects of free radicals, which are potentially damaging by-products of energy metabolism, and been shown to play a role in immune function, in DNA repair, and other metabolic processes. Sources: Wheat germ, almonds, sunflower seeds and oil, hazelnuts, peanut butter, spinach, kiwi and mango.

Vitamin C: Humans do not have the ability to make their own vitamin C which is obtained through diet. Vitamin C plays an important role in the synthesis of the neurotransmitter critical to brain function and are known to affect mood.  Vitamin C is required for the synthesis of carnitine, a small molecule that is essential for the transport of fat to cellular organelles called mitochondria, for conversion to energy.  Sources: Orange, grapefruit, strawberries, tomato, red pepper, broccoli, and potato.

Vitamin A: Vitamin A plays an important role in vision, bone growth, reproduction, cell division, and cell differentiation (in which a cell becomes part of the brain, muscle, lungs, and blood. Vitamin A helps regulate the immune system, which helps prevent or fight off infections by making white blood cells that destroy harmful bacteria and viruses. Vitamin A also may help lymphocytes (a type of white blood cell) fight infections more effectively. Vitamin A promotes healthy surface linings of the eyes and the respiratory, urinary, and intestinal tracts. Vitamin A also helps the skin and mucous membranes function as a barrier to bacteria and viruses.  Sources: Chicken liver, beef liver, carrots, spinach, kale, cantaloupe, apricots, papaya, mango, oatmeal, milk, cheese, eggs, peas, tomato, peaches, and pepper.

Magnesium: Magnesium is the fourth most abundant mineral in the body and is essential to good health. Magnesium is needed for more than 300 biochemical reactions in the body. It helps maintain normal muscle and nerve function, keeps heart rhythm steady, supports a healthy immune system, and keeps bones strong. Magnesium also helps regulate blood sugar levels, promotes normal blood pressure, and is known to be involved in energy metabolism and protein synthesis. There is an increased interest in the role of magnesium in preventing and managing disorders such as hypertension, cardiovascular disease, and diabetes. Sources: Halibut, almonds, cashews, spinach, oatmeal, potato, peanuts, peas, yogurt, rice, lentils, avocado, beans, banana, milk, whole wheat bread, and raisins.           

Zinc: Zinc is an essential mineral that is found in almost every cell. It stimulates the activity of approximately 100 enzymes that promote biochemical reactions in your body. Zinc supports a healthy immune system, is needed for wound healing, helps maintain your sense of taste and smell, and is needed for DNA synthesis. Zinc also supports normal growth and development during pregnancy, childhood, and adolescence.  Sources: Oysters, beef, chicken, yogurt, beans, cashews, pecans, almonds, walnuts, milk, cheese, peas, and oatmeal.

Chromium: Chromium is a mineral required in trace amounts. Chromium is known to enhance the action of insulin, a hormone critical to the metabolism and storage of carbohydrate, fat, and protein in the body. Sources: Broccoli, grape juice, potato, garlic, basil, turkey, apple, banana, whole wheat bread, and green beans.

Omega-3 and Omega-6 Fatty Acids:  These fatty acids are considered essential fatty acids not produced by the body. These essential fatty acids are important for visual and neurological development, reductions in cardiovascular disease risk, and may be beneficial to individuals with diabetes.  Sources: Herring, salmon, sardines, walnuts, flaxseed, oysters, trout, and shrimp.

Selenium: Selenium is important but required only in small amounts. Selenium is incorporated into proteins to make selenoproteins, which are important antioxidant enzymes that help prevent cellular damage . Other selenoproteins help regulate thyroid function and play a role in the immune system. Sources: Brazil nuts, tuna, beef, pasta, cod, turkey, chicken, eggs, cottage cheese, oatmeal, rice, whole wheat bread, walnuts and cheese.

Vitamin K: Vitamin K is important in blood clotting, bone mineralization and cell growth. Sources: Kale, broccoli, spinach, olive oil, canola oil, parsley, and lettuce.

For a healthy, balanced diet that encompasses all of these macronutrients and micronutrients, refer to the Death to Diabetes Super Meal Model.

Conclusion: Diet Alters Gene Expression

Dietary chemicals have been shown to alter gene expression in a number of ways. For example, they may:

• act as ligands for transcription factor receptors
• be metabolized by primary or secondary metabolic pathways thereby altering concentrations of substrates or intermediates or
• alter signal transduction pathways

Exogenous nutrients can affect gene expression directly (A) or indirectly (B and C in Figure).

This was convincingly demonstrated by comprehensive investigation of yeast gene expression using microarrays.  A diauxic shift from fermentation respiration resulted in, metabolic reprogramming that identified genes previously unassociated with nutrient utilization.

Although more complex than yeast, we believe the constellation of genes that make up the human genome respond in a similar fashion to the dietary chemicals.

References

Guo, S and Sonenshein, G.  (2006)  Green Tea Polyphenols and Cancer Prevention. In Nutritional Genomics: Discovering the Path to Personalized Nutrition.  Kaput, J and Rodriguz, R (eds). Wiley and Sons, Inc. NY. 2006. pp 175 - 206.

Kaput, J. and Rodriguez, RL.  2004. Nutritional genomics: the next frontier in the postgenomic era.  Physiological Genomics 16, 166 - 177 (free access)

Magbuana, MJM, Dawson, K, Huang, L, Malyj, W, Gregg, J, Galvez, A, and Rodriguez, RL (2006) Nutrient - gene Interactions Involving Soy Peptide and Chemopreventive Epithelial Cells In Nutritional Genomics: Discovering the Path to Personalized Nutrition.  Kaput, J and Rodriguz, R (eds). Wiley and Sons, Inc. NY. 2006. pp 255 - 276.

Schuster, GU.  (2006) Nutrients and Gene Expression.   In Nutritional Genomics: Discovering the Path to Personalized Nutrition.  Kaput, J and Rodriguz, R (eds). Wiley and Sons, Inc. NY. 2006. pp 153 - 173