© Whole Foods Magazine

October 2007


Antioxidants, Inflammation, Facial Wrinkles and Weight Loss

An interview with Nicholas V. Perricone, M.D.

By Richard A. Passwater, Ph.D.


Antioxidant nutrients have been my professional passion since 1959. My research with antioxidant nutrients has centered on preventing cancer and heart disease and slowing the aging process. Although skin wrinkling is part of the aging process, this is not my concern with the health benefits of slowing the rate of aging. I was not too surprised to read of the research of Dr. Nicholas V. Perricone and his use of antioxidant nutrients for skin health. However, I was surprised to see where he has found that antioxidant nutrients not only slow the wrinkling of skin, but also can reverse it. That isn’t an antioxidant effect.

So, I was curious. What could be going on in the skin with antioxidants beyond slowing the effects of sunlight and free radicals in causing skin to wrinkle? How could they reverse wrinkling? When I looked at Dr. Perricone’s research and saw where he was having such good results with alpha-lipoic acid and some of my other favorite antioxidant nutrients, I was hooked. I had to learn more. What Dr. Perricone showed me about the mechanisms involved was extremely interesting. I hope you find his research as interesting as I have.



Nicholas Perricone, M.D., FACN, is a board-certified clinical and research dermatologist, and CEO of NV Perricone MD, Ltd. A brilliant scholar, Dr. Perricone completed medical school in just 3 years, graduating with distinction. He completed his internship in pediatrics at Yale Medical School and his dermatology residency at Ford Medical Center.

Dr. Perricone is an adjunct professor of medicine at Michigan State University’s College of Human Medicine. He is certified by the American Board of Dermatology, is a fellow of the New York Academy of Sciences, and is a fellow of the American College of Nutrition. He also is a fellow of the American Academy of Dermatology and the Society of Investigative Dermatology. Dr. Perricone has served as assistant clinical professor of dermatology at Yale School of Medicine and as chief of dermatology at the state of Connecticut’s Veterans Hospital.

Dr. Perricone’s latest book, AGE-less Face, AGE-less Mind (Ballantine Books), is scheduled to be released about October 30, 2007. This book expands upon his research and explains one of the cardinal processes of aging, apart from the inflammatory cascade initiated by free-radical damage. The “AGE-less” is in reference to the process that creates advanced glycosylation end products, appropriately known as AGEs.


Passwater: As a dermatologist, what aroused your interest in nutrition and skin?


Perricone: During medical school and my three-year residency in dermatology, I made some important connections between inflammation and disease. In order to learn about hundreds of skin diseases we studied in books, we had to recognize them in the clinical examination of patients and be able to identify diseases under a microscope. When studying various forms of skin cancer, I noticed that every time I saw a skin cancer under the microscope, inflammation was present.

It wasn’t just cancer and pre-cancer that showed inflammation under the microscope. When I looked at a biopsy of skin that showed clinical signs of aging, inflammation was present. Skin that showed no clinical signs of aging showed no inflammation. This discovery so intrigued me that I began to find endless ways to put my emerging theory to the test.

When we examine inflammation under the microscope, it has an unmistakable, characteristic appearance. To make it visible, we stain the slide. The inflammation shows as little dark blue dots, almost like confetti—although the presence of inflammation is nothing to celebrate. Quite the opposite is true.

This “confetti” is present when we look at aging skin. I was puzzled about why this inflammatory response was occurring. I wondered if inflammation was actually causing these changes in the skin. I began to consider wrinkles as a disease, since inflammation was always present when damage to skin tissue resulted in wrinkles. I was driven by a number of questions. Were the negative signs of aging just a normal, unavoidable fact of life? Or were they an abnormal condition caused by an inflammatory state? Could many of the visible effects of aging be greatly reduced or avoided altogether?

My professors thought inflammation was just a part of the whole picture—a byproduct and not the cause. For example, your thumb turns red and swollen after you accidentally hit it with a hammer. Ironically, one of the cornerstones of dermatologic therapy is cortisone, which is, of course, an anti-inflammatory. The tongue-in-cheek description of dermatological practice is that if you see a skin disease, and it is wet, you dry it; if it is dry, you wet it; and if you don’t know what it is, you treat it with steroids (cortisones), which are powerful anti-inflammatories. I could not understand why the medical establishment refused to make the connection.

I knew what I saw and never let that go. I continued to believe that inflammation was at the root of cancer and other acute and chronic diseases. Whenever I looked under microscope at a disease, everything from arthritis to heart disease, inflammation was always a component. Steroids did come with the high price of serious and often dangerous side effects. Although steroids might be indicated in certain dermatological conditions, their anti-inflammatory properties were not traditionally recommended for most diseases. Since I believed that inflammation was the basis for disease, my goal was to find anti-inflammatories that could stop, treat and reverse the symptoms without doing harm.

Naturally, my first step as a dermatologist was to search for ways to control inflammation in the skin. Every skin problem or disease I saw had an inflammatory component to it. Our skin is constantly assaulted from inside and out with elements that create inflammation: sun exposure, air pollution, harsh soaps and skincare products, internal disease, stress lack of sleep, sugar consumption, dehydration—the list could go on. The leading cause of inflammation that should top that list is sugar and foods that rapidly convert to sugar, known as high-glycemic carbohydrates. (Sugar’s ravishing effects are discussed in the next chapter.) My research has been focused on disarming these threats to healthy skin. The program I have developed is designed to fight inflammation by means of a synergy of diet, supplements, skincare and exercise. To understand why my recommendations work, you have to know the mechanics of inflammation and its connection to aging and disease.


Passwater: You not only have a dermatology practice, but you also do research and publish in the scientific and medical literature. What are your research interests?


Perricone: I am very interested in therapeutic, natural methods to reduce inflammation in the body. This encompasses many areas from the search for anti-glycating agents to modifying peptides and other molecules to ensure that they aren’t degraded when used therapeutically. I am also working with other areas including light therapy, electronic muscle stimulation and so forth.


Passwater: What were the findings in your practice that lead to your 1998 book, The Wrinkle Cure: Unlock the Power of Cosmeceuticals for Supple Youthful Skin?


Perricone: Every disease I studied had a common theme: whether it was cancer or aging, inflammation was present. I was convinced that inflammation was not just a secondary response. I believed inflammation to be the key to the whole process of disease of every type.

This powerful conviction led me to develop an inflammation–aging theory and an inflammation–cancer theory that have been the basis of my research for decades. I realized that regardless of where a disease originated, regardless of its root cause, anti-inflammatories would often solve the problem or at least diminish the symptoms.

Acute inflammation is a protective response of tissue to irritation, injury or infection, and is characterized by pain, redness, swelling and sometimes loss of function. It is, under normal circumstances, beneficial and helps the body repair the effects of trauma or infection. However, prolonged, excess or chronic inflammation becomes harmful.

When low-grade invisible inflammation occurs in the very cells that comprise our organ systems, a concept I introduced in my first book, The Wrinkle Cure (2000), we are placed at great risk for a host of degenerative, age-related diseases. This is because cells that are attacked by self-generated inflammation will not function properly (meaning that we did something to precipitate a pro-inflammatory response in our cells, thus causing malfunction and sometimes complete breakdown).

In other words, cells respond to the way we treat them. If we keep them healthy and free of injury, if we give them the proper nourishment, they keep us alive and running at top form. If we don’t—if we expose them to too much sun, to environmental toxins, to extended periods of stress or to high-glycemic sugars and starches—the cells will react by producing inflammatory chemicals as a deviation of the normal defense mechanism. And if we mistreat our cells in this way on a regular basis, we can end up with organ system failure,


Passwater: You expanded your nutritional advice in The Perricone Prescription: A Physician’s 28 day Program for Total Face and Body Rejuvenation in 2002 to advise readers how not only to improve wrinkles, but also to fight chronic subclinical inflammation that can result in diseases ranging from Alzheimer’s to arthritis. You followed this with The Perricone Promise: Look Younger, Live Longer in Three Easy Steps in 2004. What are the three easy steps? What are your teachings from these books?


Perricone: My decades of research has shown that The Inflammation/Aging Connection is the single greatest precipitator of aging and age-related diseases such as heart disease, diabetes, Alzheimer’s disease, arthritis, certain forms of cancer and wrinkled, sagging skin.

This inflammation is sub-clinical (invisible to the eye) and takes place on a cellular level. It does its damage by triggering free radicals, which accelerate aging by damaging cells. This inflammation may be caused by:

*eating a pro-inflammatory diet (i.e., high-glycemic carbohydrates);

*environmental stressors;

*a weakened immune system;

*excess exposure to ultraviolet light;

*hormonal changes; and


We can control inflammation in our bodies by following a three-tiered program designed to carefully control our blood sugar and insulin levels. To do so, we must avoid foods that provoke a “glycemic” response in the body (i.e., cause a rapid rise in blood sugar). This is the key to health, longevity, mental clarity, well-being and beautiful youthful skin. Foods that are pro-inflammatory, such as all forms of sugar, processed foods, pasta, breads, pastry, baked goods, and snack foods such as rice and corn cakes, chips, pretzels, etc., cause a highly destructive pro-inflammatory response in our bodies. The result? The acceleration of the aging process of all organ systems in our body, including the skin, causing an increased risk of degenerative disease and inflexible, wrinkled, sagging skin.


Tier One:

The Anti-Inflammatory Diet

The anti-inflammatory diet is the cornerstone of the Perricone Program. It consists of the following components:

*high-quality protein, like that found in fish, shellfish, poultry and tofu;

*low-glycemic (will not provoke a glycemic response when consumed in moderation) carbohydrates, including colorful fresh fruits and vegetables and whole grains such as old-fashioned oatmeal, legumes such as beans and lentils;

*healthy fats such as those found in cold water fish (especially wild Alaskan salmon, halibut, sardines, herring, anchovies, etc.), nuts, seeds, and olive oil;

*8–10 glasses of pure spring water per day;

*anti-oxidant rich beverages such as green tea.

These foods and beverages act as natural anti-inflammatories and help to maintain normal levels of insulin and blood sugar. The incomparable health and beauty benefits of the anti-inflammatory diet are visible in just three days.


Tier Two:

Nutritional Supplements

I recommend a variety of unique nutritional supplements in addition to the complete spectrum of vitamins and minerals recommended by nutrition experts worldwide (B-complex, vitamin E, calcium–magnesium, etc.). Dr. Perricone’s research has shown that nutrients that possess anti-oxidant properties act as natural anti-inflammatories. This is important because anti-oxidants are nature’s anti-inflammatories. Designed to work synergistically to enhance the benefits of the anti-inflammatory diet, these nutrients offer anti-aging, anti-inflammatory, fat metabolizing and peptide boosting benefits and help prevent and reverse oxidative damage on a cellular level, of critical importance as we age.

Recommended active ingredients include:

*alpha lipoic acid;

*vitamin C ester;

*dimethyl amino ethanol (DMAE);

*coenzyme Q-10;

*conjugated linoleic acid;


*L-carnitine fumerate;

*N-acetyl carnitine;







Tier Three:

Clinical Skincare

In addition to creating vibrant skin and optimum health through diet and supplements, topical anti-oxidants can work synergistically to enhance the natural health and beauty of your skin. Dr. Perricone’s research has shown that many food-based nutrients provide anti-inflammatory as well as anti-oxidant activity when applied topically. Optimum results are achieved when they are used as part of the three-tiered program (i.e., diet, supplements, topicals). The unique, patented ingredients that comprise the NV Perricone MD line of Cosmeceuticals have been painstakingly formulated to deliver powerful, efficacious benefits to the skin, resulting in a smooth, youthful, supple, toned and radiant appearance to face and body.

The following substances have been shown to significantly improve the appearance of skin when added to topical formulations:

*alpha lipoic acid;

*dimethyl amino ethanol (DMAE);


*olive oil polyphenols;



*vitamin C ester;



Passwater: We discussed how sub-clinical inflammation causes illness as well as wrinkles and other skin problems. How does it affect body fat? You addressed this in your 2005 book, The Perricone Weight-Loss Diet: A Simple 3-Part Plan to Lose the Fat, the Wrinkles, and the Years.


Perricone: The Perricone Weight-Loss Diet made the connection between inflammation and body fat (and the fact that one is never present without the other). Insulin is an important hormone that helps the body utilize blood sugar for energy or store it as glycogen or fat. But if the insulin is released too quickly, it has a pro-inflammatory effect. After a rapid rise in blood sugar, there will be a precipitous drop in blood sugar, resulting in feelings of hunger, which can lead to vicious cycle of overeating. This is why a diet centered on breads, baked goods, snack foods, sweets and other sugary, starchy foods results in unwanted weight gain and great difficulty in losing the weight. Ironically, in this instance, it is not the caloric value of the foods causing the weight gain. In fact, a rice cake only has around 40 calories. However, because it is rapidly converted to sugar in the blood stream, resulting in the insulin release, it will cause you to store body fat. An insulin release can result in the storage of body fat.

This past decade has seen a complete turnaround in the way scientists regard white adipose tissue—better known as body fat. No longer do we look upon body fat as just an inert deposit of fat cells, stored as the result of overeating. Science is discovering that body fat is not a simple cosmetic problem. We are now beginning to define body fat as a group of cells communicating with other organ systems such as the brain, the liver, the bone marrow, skeletal muscle, the adrenal cortex, the sympathetic nervous system and the complete immune system. And, the message they are communicating is not good.

In fact, these areas of fat storage function as an active endocrine organ. This body fat is actually producing hormones, just like our pancreas, thyroid, parathyroid, adrenals, pineal, pituitary and testes/ovaries, the organs that comprise the endocrine system.

Unfortunately, unlike our other organs, this agglomeration of fat cells that has become an active endocrine organ, has the unique distinction of being the only endocrine organ to send pro-inflammatory and destructive signals to all organ systems throughout the body.

This is extremely important because the body fat itself controls how much body fat is going to be stored. And the more body fat we have, the more body fat we will store. This becomes even more frightening when we begin to understand that the greater amount of fat we have stored, the greater its negative influence on the entire body; an extremely destructive, inflammatory influence. It also negatively impacts our appetite, our energy expenditure and our immune system.

We need to learn how to control our blood sugar and insulin levels. This will prevent a large insulin response, which in turn causes an inflammatory cascade and inhibits cellular rejuvenation. But, insulin affects more than our ability to stay slim. It also affects our skin.

Insulin is a critical hormone—too much of it circulating in the blood stream will:

* accelerate aging both internally and externally;

* promote weight gain and obesity by putting a “lock” on body fat;

* shrink muscle mass in both face and body, resulting in a tired, droopy, sagging face, eye area, neck, jaw line and the loss of that healthy toned look from good muscle tone in upper body, midriff, thighs, etc.

To prevent the aging effects of elevated insulin take the following steps:

* Follow an anti-inflammatory diet.

* Avoid sugar and starchy foods.

* Eat the right fats to burn fat.

* Stabilize blood sugar and insulin.

* Eat your protein first at the start of every meal or snack.


Passwater: Well, we are not yet up to your most recent book and a new one is about to be released. So, let’s pause here and pick up the story of your research next month. WF


© 2007  Whole Foods Magazine and Richard A. Passwater, Ph.D.

This article is copyrighted and may not be re-produced in any form (including electronic) without the written permission of the copyright owners.