Introduction to Antioxidants

2. Introduction to Antioxidants

3. Course Author—Dr. Lester Packer, Ph.D. • Nu Skin Professional Advisory Board Member. • Ph.D. in Microbiology and Biochemistry from Yale University. Worked as Professor and Senior Researcher at the University of California at Berkeley for the past 40 years. • Has held offices as President of the International Society of Free Radical Research, President of the Oxygen Club of California, and Vice President of UNESCO’s Global Network on Molecular and Cell Biology. • Has published over 700 scientific papers and 70 books on antioxidants and health.

4. Did You Know? Many of the processes we call "aging" can be considered manifestations of the minute, cumulative effects of free radical damage on cells and tissues in the skin, heart, blood vessels, brain, etc. Find out how to prevent free radical damage in this course.

5. Objectives After viewing this course, you should have an understanding of the following: • Free radicals. • Antioxidants. • How free radicals damage cells and tissues and contribute to the aging process. • How antioxidants help fight free radical damage and can help prevent the visible signs of aging. • Technical explanation of how free radicals and antioxidants function.

6. Introduction

7. What Are Free Radicals? Mitochondria Free radicals are highly reactive, unstable molecules that cause damage to healthy cells, leading to internal aging as well as visible signs of external aging. Cell DNA Unstable free radicals

8. What Are Antioxidants? Antioxidants are molecules capable of defending our cells from free radical damage. Since free radicals are not only created in the environment, but also in our bodies, a continuous supply of antioxidants is critical for internal and external health and longevity. Antioxidants defend cells. Free radicals

9. Example of Free Radical Damage: The First Wrinkle We come into this world with healthy cells, but every day the negative effects of free radicals add to the damage of the previous day. Each day, our young, healthy skin is exposed to trillions of free radicals from a variety of sources, such as the sun’s ultraviolet rays, pollution, smoke, internal processes, and external stress.

10. The First Wrinkle Overexposure to free radicals damages not only our cells’ ability to function, but also the integrity of our cells’ overall composition, resulting in a next generation of cells that is less healthy and less productive than the cells they came from.

11. The First Wrinkle Epidermis In the case of our skin cells, this can mean, over time, our fibroblasts—cells responsible for collagen and elastin production—will be working less efficiently to produce the skin proteins necessary for skin smoothness, firmness, and elasticity. Dermal - Epidermal Junction Mast Cell Dermis Elastin Fiber Collagen Fiber Glycosaminoglycans Fibroblast Cell Blood Vessels

12. The First Wrinkle Although this is happening gradually beneath the outermost surface of our skin, this decrease in collagen and elastin production becomes visible sometime in our late twenties or early thirties when we look in the mirror and discover our first wrinkle.

13. Sources of Free Radicals

14. Sources of Free Radicals Free radicals—unstable, highly reactive compounds—are created inside our bodies through normal, necessary chemical reactions and all around us through pollution, UV radiation, x-rays, stress, strenuous exercise, and smoking. Smoking can be particularly harmful: Each cigarette releases 10 quadrillion free radicals into the lungs. This is why smokers age so much faster than non-smokers.

15. How Free Radicals Age the Skin

16. Free Radical Damage Damaged Cell Free radicals damage lipids, proteins, and DNA. DNA is present in the nucleus of almost every cell, stores all genetic information, and dictates cellular functions. The damage done to lipids, proteins, and DNA by free radicals is the root cause of aging. Free radicals damage lipids, proteins, and DNA

17. Free Radical Damage Every day, the DNA in a single cell receives thousands of free radical assaults. Fortunately, our cells have repair enzymes that fix most of this damage. As we get older, the delicate balance between damage and repair becomes unbalanced. When cells with damaged DNA replicate, they create cells with imperfect structure and a compromised ability to function. DNA damage Nucleus Free radicals damage DNA

18. Cellular Damage Mitochondria In addition to the molecular DNA damage caused by free radicals, they also cause damage to other basic cellular structures such as mitochondria—structures inside the cell responsible for cellular energy production. If one considers the cell as a small factory, the mitochondria would be the thousands of tiny power generators that enable the cell to function properly. DNA Damaged cell Free radicals damage lipids, proteins, and DNA

19. Cellular Oxidation Mitochondria When scientists talk about the effect of free radicals on cellular components, such as DNA or mitochondria, they say the structure has been “oxidized.” When cell structures are oxidatively damaged by free radicals, the health of the entire cell is weakened. DNA Cell structures are oxidized.

20. Antioxidants Are Anti-Aging

21. Antioxidants Antioxidants are a category of nutrients that have the ability to fight cell-damaging free radicals. By defending our cells against free radicals, antioxidants can help slow the internal and external aging processes. Antioxidants neutralize free radicals Neutralized free radicals

22. Antioxidants There are hundreds of known antioxidants, many of which are derived from plants. Plants, to protect their constantly exposed tissues from free radicals, have developed free radical fighting phytochemicals as a natural defense system. Each plant contains hundreds of phytochemicals, many of which provide antioxidant protection and fulfill many other essential functions. Carotenoids, polyphenols, and flavonoids are some examples.

23. Skin Beneficial Antioxidants

24. Key Antioxidants CH3 OH CH3 CH3 • Vitamin antioxidants • Carotenoids • Phenolic Compounds • Flavonoid polyphenols • Other key antioxidants • Coenzyme Q10 • Alpha lipoic acid CH3 O CH3 CH3 CH3 CH3 Vitamin E OH HO O HO OH Hydroxytyrosol S S Alpha Lipoic Acid

25. The Antioxidant Network Antioxidants rely on a network for protection and support. Antioxidants work together to fight free radicals directly or to regenerate and support other antioxidants. In the antioxidant network, carotenoids are the first line of defense. By destroying free radicals, carotenoids protect and enable other antioxidants to perform their more specific and critical functions.

26. The core of the antioxidant network includes powerful antioxidants such vitamins E, C, and CoQ10. In addition to their free radical fighting properties, these antioxidants have other functions that allow them to make critical contributions to our health and longevity. The Antioxidant Network Vitamin C CoQ10 CoQ10 Vitamin C Vitamin E Vitamin E (Carotenoids) Carotenoids enable other antioxidants to perform more specific functions

27. Vitamin Antioxidants—Vitamin E Vitamin E is one of the body’s most important fat-soluble antioxidant nutrients. Vitamin E protects healthy cell membranes (largely composed of fatty acids) from oxidative free radical damage. There are eight natural forms of vitamin E (four forms of tocopherols* and four tocotrienols). CH3 OH CH3 CH3 CH3 O CH3 CH3 CH3 CH3 Vitamin E *Ingredients in skin care formulations that contain a variation of the name tocopherol (e.g., tocopheryl acetate and tocopheryl lineate) are forms of the antioxidant vitamin E.

28. Vitamin Antioxidants—Vitamin C Vitamin C (ascorbic acid*) is water-soluble, enabling it to scavenge free radicals in aqueous (watery) environments, such as the inside of our cells and extracellular body fluids. Vitamin C works synergistically with vitamin E to quench free radicals and also works to regenerate vitamin E, keeping it active. * Ingredients in skin care formulations that contain a variation of the term ascorbic (e.g., ascorbyl palmitate) are forms of vitamin C.

29. Carotenoids Carotenoids are a major class of phytonutrients. Examples of carotenoids are beta-carotene, alpha-carotene, lutein, and lycopene. They are natural, fat-soluble pigments found principally in plants and algae, where they play a critical role in protecting and aiding the photosynthetic process. Carotenoids are responsible for many of the red, orange, and yellow hues of plant leaves, fruits, and flowers.

30. Carotenoids Carotenoids—sometimes referred to as the first line of defense—provide critical antioxidant protection to cells and other antioxidants by absorbing or “blotting up” large amounts of attacking free radicals. This allows other antioxidants to function in more specialized ways.

31. Phenolic Compounds Just as plants produce lipid-soluble carotenoids to protect cellular structures composed mostly of lipids, plants also produce phenolic (ring-like structure) compounds to guard their tissues against free radical damage. These compounds can be fat or water-soluble. Examples of phenolic compounds are hydroxytyrosol in olive oil (one phenolic ring) and polyphenols (multiple phenolic rings) in strawberries. OH HO HO Hydroxytyrosol (one ring)

32. Flavonoid Polyphenols Flavonoids are a class of polyphenolic compounds, containing multiple ring structures. It is estimated that there are over 600 different flavonoids present in foods and beverages. Some common flavonoids are catechins (green tea), quercetin, proanthocyanidins (grape seed extract), and soy isoflavones. Flavonoids provide increased cell protection for the DNA as well as promote the repair of DNA damaged by free radical oxidation. Phenolic Ring Structure HO OH OH OH O OH OH O C OH O OH Flavonoid Polyphenol (multiple rings)

33. Other Key Antioxidants—Alpha Lipoic Acid Alpha lipoic acid is a naturally occurring molecule in plants and animals that has the ability to neutralize free radicals. Another important function of alpha lipoic acid is its ability, when applied topically, to improve skin tone and texture. O OH S S Alpha Lipoic Acid

34. Other Key Antioxidants—CoQ10 O Coenzyme Q10, or CoQ10, is found naturally in our cells; however, CoQ10 levels in the body have been shown to decline after age 20. Highly concentrated within the cell’s mitochondria, CoQ10, like vitamins C and E, quenches free radicals and helps regenerate other antioxidants. CH3 H3CO H H3CO CH3 O 10 CoQ10 Additionally, CoQ10 plays an important role as a co-enzyme in generating cellular energy and offers critical protection to the mitochondria (power generators) in all cells.

35. Internal and External Supplementation Just as health and nutrition experts recommend a high intake of antioxidants from a variety of fruits and vegetables and nutritional supplements, skin care experts are now recognizing the anti-aging benefits of topically applied antioxidants. Recent scientific studies have shown that supplementing internally and topically with antioxidants results in higher overall antioxidant levels than either delivery method alone.

36. Some skin care products offer antioxidant benefits directly to the skin by including antioxidant-rich vitamins and extracts in their formulations. While carotenoids have typically not been included in skin care products due to their intense color, a unique form of colorless carotenoids with enhanced UV-protective properties has been discovered. Topical Antioxidants

37. Review—Key Antioxidants • Vitamin antioxidants • Vitamin E • Vitamin C • Carotenoids (e.g., beta-carotene, alpha-carotene, lutein, and lycopene). • Phenolic Compounds (e.g., hydroxytyrosol in olive oil and phytochemicals in strawberries). • Flavonoid polyphenols (e.g., green tea catechins, grape seed proanthocyanidins, and soy isoflavones). • Other key antioxidants • Coenzyme Q10 • Alpha lipoic acid

38. Review—Antioxidants and Free Radicals • Free radicals are highly unstable, reactive molecules. • Free radicals damage the DNA within cells. This damage is passed on to newly replicated cells. Over time, genetic damage builds up and interferes with healthy cell function. • Antioxidants are natural compounds found in fruits and vegetables that fight free radicals, thereby neutralizing their negative effects. • Some key antioxidants are vitamins E and C, carotenoids, flavonoids, alpha lipoic acid, and CoQ10.

39. Technical Appendix: How Free Radicals and Antioxidants Function

40. e- e- J How Free Radicals Damage Cells Free radicals are unstable, highly reactive molecules because they have one or more unpaired electrons. Note: every atom has protons (positively charged) and neutrons (neutral) in their nucleus, with electrons (negatively charged) circling around the nucleus. e- e- L Unstable free radical Stable atom

41. How Free Radicals Damage Cells In order to stabilize themselves, free radicals seek ways to pair their unpaired electrons. To do this, they may steal electrons from other stable molecules. e- e- e- e- L J Free radical stealing electrons from a stable atom.

42. How Free Radicals Damage Cells This can cause the secondary molecule to become a reactive, unstable free radical. e- e- e- e- J L Unstable free radical

43. How Free Radicals Damage Cells Having lost its electron, these secondary molecules become free radicals that, in turn, steal electrons from other molecules. e- e- e- e- e- e- J L J Unstable free radical

44. How Free Radicals Damage Cells This cascading effect sets off a free-radical chain reaction of molecular destabilization. e- e- e- e- e- e- J L J Free radical chain reaction

45. How Free Radicals Damage Cells Free radical chain reactions can continue indefinitely, ultimately damaging millions of cells. e- e- e- e- e- e- J J L

46. e- e- L Free Radical Damage Much of what is damaged by free radicals are DNA, lipids, and proteins that make up the cellular structures in our bodies. Unstable free radical Cell

47. e- e- J Free Radical Damage Among other serious consequences, this damage leads to side effects associated with skin-aging, such as poor cell renewal, and slowed collagen and elastin production. Damaged cell

48. How Antioxidants Work

49. How Antioxidants Work Antioxidants are stable molecules with electrons to spare or with the ability to receive extra electrons. e- e- J e- Antioxidant

50. e- e- e- e- J L e- How Antioxidants Work Antioxidants are nature’s defense against the damaging effects of free radicals. They guard cellular structures and DNA against electron-scavenging free radicals. Unstable free radical Antioxidant protecting the cell.