Introduction to Nutrigenomics
A question often posed to me during lectures and public appearances is the following: “Dr. Perricone, isn’t it true that genetics play a huge role in my susceptibility to disease and signs of aging?”
Some people ask this question because they want to avoid taking responsibility for their health – assuming that, for good or ill, it is fixed in their genes like their height or their eye color.
As you will discover in this book, this is far from true. We have a great deal more control of our bodies than previously thought. There is an emerging field of study known as nutrigenomics. The word is a combination of nutrition and genomics. Together, they describe a field that focuses on the relationship between diet and gene expression. Nutrigenomic research investigates questions such as how food influences gene expression and how genes influence the way individuals absorb and metabolize different types of nutrients.
Using nutrigenomics, I will demonstrate how you can actually change the way genes are expressed and how that information is transmitted, simply by manipulating different aspects of your diet and lifestyle. For example, you know that by eating many of the foods included in my anti-inflammatory diet, you can:
1. Switch on protective genes
2. Switch off genes that may have a negative effect on our health
In this chapter we are going to introduce substances that turn off disease and age-accelerating transcription factors such as NF‑кB and AP‑1 and turn on the age- and disease-fighting transcription factor NRF2. This not inconsiderable feat is accomplished by a class of exotic-sounding substances known as Michael acceptor pharmacophores. This process is one of the most fascinating and exciting aspects of my research during the past decade. The remarkably protective properties of Michael acceptor pharmacophores are one of our finest strategies for staying Forever Young. In addition, I will introduce you to phytonutrients with other pharmacophores, which act as powerful anti-inflammatories through similar mechanisms.
In many of my books, I have discussed transcription factors, the protein messengers in our cells that are activated or silenced by different stimuli. Upon activation, these transcription factors translocate to the nucleus of the cell, where they attach to receptor sites on the genes and upregulate, or turn on, their expression. Gene expression provides us with a new strategy to suppress pro-inflammatory genes. This is critical because, as you know, inflammation is the common denominator of all the problems we see with aging and age-related disease.
But research has shown us that it is not just the transcription factors that play a role in gene expression; we now know that nutrients can also affect gene expression in many ways. My research has revealed a number of novel compounds, naturally found in our diet, that can powerfully and positively affect gene expression.
When these nutrients up regulate gene expression, the following benefits result:
- Healthy body weight
- Resistance to cognitive decline
- Decreased incidence of cancer
- Prevention and reversal of insulin resistance and metabolic syndrome
- Maintenance of bone density
- Optimal function of all vital organs, including the heart, kidney, spleen, and immune system
- Maintenance of muscle mass
- Well-functioning endocrine system that keeps us fit and sexually active into our later years
- Prevention and reduction of damage to the skin caused by aging and the environment
These lofty claims may sound unrealistic, but when it comes to nutrigenomics, the results are well documented.
Activating the Longevity Factors
Thanks to my appearances on public television, Oprah, GMA, the Today show, and other popular venues, many people refer to me as the “Salmon and Blueberry Doctor.” It is true that wild salmon and blueberries held center stage in my first book, The Wrinkle Cure, in which I introduced the anti-inflammatory diet. There are many reasons for this. Salmon and the other cold-water fish are an outstanding source of high-quality protein; carotenoid antioxidants, like astaxanthin, which you will read about in chapter 4; and high levels of the omega-3s and other essential fats, all of which have powerful anti-inflammatory effects.
Roses Are Red, Violets Are Blue (Thanks to the Anthocyanins)
Blueberries are also antioxidant powerhouses containing a variety of phytonutrients, including anthocyanins, from the Greek anthos, meaning “flower” plus kyanos, meaning “blue.” Anthocyanins may be the most important of the visible plant pigments, responsible for the reds, purples, and blues you see in plants that have strong antioxidant properties. They are found in such fruits as blueberries, blackberries, raspberries, black raspberries, black currants, açai, and chokeberry and vegetables including red cabbage, watercress, and eggplant. Anthocyanins provide many different functions for the plant. They are antioxidants, protect the plant against UV light, are a defense mechanism, and have an important role in pollination and reproduction. The purple pansy, for example, owes its color to anthocyanins, which attract insects to propagate the species.
As antioxidants, anthocyanins protect plants from free radicals produced by sunlight or damage to the plant. The ability of the anthocyanins to protect plants from free-radical damage can also benefit us when we eat foods that are rich in anthocyanins.
As mentioned earlier in this chapter, blueberries contain many powerful polyphenols that make them a true superfood, one that I have been recommending for decades. We know that they are rich in polyphenols such as the anthocyanins, which have many benefits, including the following.
- They have the ability to speed up neural communication. Blueberry-supplemented neurons have a better ability to communicate with each other.
- Catechins contained in blueberries prevent cell death and the loss of nerve growth factors.
- Blueberries increase the release of dopamine, an energizing, stimulatory neurotransmitter.
- Blueberries protect us from age-associated declines in dopamine levels, helping us to maintain youthful brain function.
Anthocyanins also possess a special form of stilbenes known as pterostilbene, which activates the genes that influence longevity factors. This is another reason choosing brightly colored fruits and vegetables is essential. The colors signify the presence of plant pigments, which do more than just add color to fruits, vegetables, and certain seafood. Colorful fruits and vegetables serve as the top dietary sources of disease-preventive phytonutrients and antiaging antioxidants. But, this is not the entire story. We now know that many of these phytonutrients also work through other mechanisms, specifically the expression of genes that can upregulate the natural protective mechanisms of our cells.
Superfoods and Spices for Beautiful Skin
I believe that foods have an extremely powerful effect on our physical and mental well-being. Functioning very much like pharmacological agents, foods can dramatically alter the biochemistry of cells, affecting both cell and organ function. Food is what provides the body with the nutrients needed for cellular growth and repair. As we age, cellular inflammation disrupts the cell’s normal biochemical functions, negatively affecting all organ systems. We know that the high-glycemic carbohydrates – sugars and starches – cause a rapid rise in blood sugar and insulin and generate an inflammatory response. In addition, synthetic foods like trans fats and other chemical additives disrupt cellular function by either increasing inflammation or functioning as toxins.
Inflammation and the Skin
The skin is eventually damaged by this chronic low-grade inflammation, which manifests in the classic signs of aging, including wrinkling, sagging, discoloration, enlarged pores, and lack of radiance. We long for a radiant, youthful complexion and try unsuccessfully to achieve this with a variety of cosmetics and potions that offer “hope in a jar” and not much else.
But there is good news. It has been shown that after only three days of the anti-inflammatory diet, skin looks significantly healthier, more radiant, and less wrinkled. And topical anti-inflammatories, many of them from food-sourced antioxidants, provide many visible benefits. We are now ready for the next generation of topical therapies, which rely on nutrigenomics and the marvel of gene expression.
Designer Genes for Flawless Skin
Food-based nutrients can alter gene expression. As a dermatologist, I have been delighted to learn that when these nutrients are applied topically, they can upregulate the expression of genes that decrease and/or prevent inflammation. By assisting the cells’ normal ability to repair themselves, these nutrients produce a more youthful appearance with positive, visible changes in a matter of days.
The Rainbow Foods – Color Is the Key to Gene Expression
I have long encouraged my patients to shop for the “rainbow foods” in the produce aisle. A full palette of sensual color will not only make your food beautiful, it will heal your body on a cellular level and will keep you young. Choose from the array of fresh fruits and vegetables at the market or, even better, at a local farmers’ market:
- A variety of baby greens, including watercress and arugula
- Red cabbage
- Dark green broccoli, broccoli rabe, broccolini
- String beans
- Red onions and tomatoes
- Purple garlic
- Red, purple, and yellow bell peppers
- Bright red chile peppers
- Purple eggplant
- Alfalfa and broccoli sprouts
- Fragrant fresh herbs and spices, including basil, parsley, thyme, rosemary, sage, oregano, dill, cinnamon sticks, golden turmeric root, thyme
- Deep blue blueberries
- Brilliant blackberries
- Vivid red strawberries
- Royal purple plums
- Deep red or bright green apples
- Red-black bing cherries
- Dark green extra-virgin olive oil
- An assortment of green and black olives
In the bulk food department, stock up on:
- Dark red kidney beans
- Black and red lentils
- Golden oats
- Warm brown walnuts
- Dark chocolate
- Bright green pumpkin seeds
And don’t forget seafood:
- Rich, red Alaskan sockeye salmon
- Maine lobster
- Deep pink Alaskan king crab legs
For even more on the rainbow foods, see chapter 8, “The Forever Young Kitchen and Recipes.”
All antioxidants act as anti-inflammatories, but not all phytonutrients are necessarily antioxidants. There are other important factors at work. Although antioxidants are an important part of the picture, the antioxidant hypothesis is an oversimplification of the biochemical story. Antioxidants do neutralize free radicals, but we now know that they do much more. Both antioxidants and phytonutrients have the power to alter the genetic instructions found in our genes’ DNA, which holds our genetic blueprint. Antioxidants and other nutrients can also act as signaling mechanisms in the cell. By means of gene expression, they upregulate the cell’s natural protective and regulatory functions, which then promote the visible differences that we are searching for.
Seeing Blue and Going Green:
Nutrigenomics in Action
The nutrients and other substances discussed in this chapter provide benefits that far exceed their function as antioxidants. Green, black, and white tea (Camellia sinensis), cocoa, and blueberries all contain special catechins (with active pharmacophores) that have significant effects on gene expression.
Tea has many benefits and is well known for both its anticancer and its antioxidant properties. Other positive effects include:
- The amino acid called theonine, a natural relaxant that won’t make you drowsy
- The ability to increase metabolism, resulting in the burning of body fat
- The ability to suppress the absorption of fat
- High levels of antioxidants that act as anti-inflammatories and are protective for the skin and brain, and all your organs
- The ability to improve glucose tolerance in diabetic mice, an effect that may help prevent type 2 diabetes
- High levels of an important polyphenol antioxidant, epigallocatechin gallate (EGCG), which is believed to be responsible for much of green tea’s promise in the prevention of cardiovascular disease, obesity, Alzheimer’s disease, cancer, periodontal disease, and dental cavities
- Topical application of low-dose green tea extract may help protect against UV damage, without the common side effects
What I find so exciting about substances like EGCG and related catechins is their ability to bind to the signaling molecules that either block or activate transcription factors. In other words, the EGCG found in tea can inhibit the activation of NF‑кB, thereby blocking all of the pro-inflammatory cytokines normally generated when it is activated. The EGCG may also bind to the protective transcription factor NRF2, upregulating many of our antioxidant defense systems.
Although the antioxidant activity of many of these substances may have a minor role in their protection against cancer, heart disease, Alzheimer’s disease, and wrinkles, it is not the main reason for their outstanding antiaging, chemoprotective properties. Their mild pro-oxidant effects are the real heroes, because they activate protective transcription factors such as NRF2 as they inhibit damaging transcription factors such as NF‑кB.
For example, we have known for years that blueberries improved memory and protected the skin, but it was not until the discovery of nutrigenomics that I learned their elusive mechanism of action, which can be attributed to the presence of the catechins. As with all of the substances discussed in this chapter, this mechanism of action exceeds their status as antioxidants. Their pro-oxidant activity results in the production of more than fifteen or twenty cell-protective enzymes that are produced by the activation of the genes controlled by transcription factors.
At the same time, the molecules that we thought were just antioxidants bind to and turn off transcription factors that are known to up-regulate more than a hundred inflammation-generating genes, resulting in damage to all of our organ systems. For example, when activated, age accelerating transcription factors produce a host of pro-inflammatory cytokines that can drive the formation of cancer. At the same time, the cell’s ability to turn on apoptosis (programmed cell death) is turned off. In other words, age-accelerating transcription factors prevent cancer cells from self-destruction. When the activation of these transcription factors is blocked, all of their cancer-promoting properties are turned off and apoptosis, which results in the self-destruction of the cancer cells, is turned on. All of the substances you will read about in this chapter have the ability to deactivate age-accelerating transcription factors and to activate the protective transcription factor.
Catechins such as EGCG act like Michael acceptor pharmacophores, controlling gene expression by binding with the thiols in these transcription factors. Once again, the nutrigenomic aspect of dietary substances proves to be the mechanism of action that far exceeds their antioxidant capabilities. Scientists still do not understand the significance of the sulfur-binding capability of EGCG and the other catechins, which allows them to control the very powerful transcription factors for good or ill.
Blueberries, cocoa, and tea, with active pharmacophores, are perfect examples of how nutritional factors exert control of gene expression. A pharmacophore is a set of structural features in a molecule that is recognized at a receptor site. This set of features is responsible for the molecule’s biological activity. Nutrigenomics, the common factor and theme throughout this book, clarifies, for the first time, the previously unknown mechanism of action of these food substances.
The EG CG in tea prevents the activation of collagen-digesting enzymes known as matrix metalloproteinase. This is a critical function because these enzymes are responsible for wrinkling of the skin.
The Future Is Now
Scientists working on the Human Genome Project talk of a bright future for genetic manipulation, one that will someday change our lives for the better. But I am telling you that right now, today, the rainbow foods that are gracing our dinner tables in all of their colorful, flavorful, and aromatic glory hold the key to turning on the protective, restorative genes and turning off the damaging ones. As might be expected, pro-inflammatory foods turn off the protective genes and turn on the damaging ones. As children we can get away with quite a bit and not have it show up on our face or body. However, as we age, our bodies are not so forgiving, and pro-inflammatory foods are manifested in a very visible manner: puffy eyes, wrinkled, sagging skin, enlarged pores, discolorations, dullness, acne, loss of youthful contours, and so forth.
Some nutrients pack a powerful nutrigenomic punch with many benefits. This chapter will examine the beneficial effects of watercress; essential fatty acids; cinnamon, turmeric, and other spices; chocolate; and vitamin D.
In addition, you will learn about new research on free radicals that uses spin traps, molecules that are able to catch volatile free radicals so that they can be studied.
Adapted Forever Young by Nicholas Perricone, M.D. © 2010 by Dr. Nicholas Perricone. By arrangement with Atria Books, A Division of Simon & Schuster, Inc. New York, NY 10020.