The skin game. (Special Feature).

"Your skin looks great."

Some people would do--or spend--anything to hear those words. It's no surprise that one of the top fund-raising attractions for public television stations across the country last year was an infomercial by the author of "The Wrinkle Cure."

What may be a surprise is that the "cure" turns out to be an untested regimen of diet, expensive supplements, and even more expensive cosmetics (see p. 6).

Is there any food you can eat, supplement you can take, or nutrient-rich lotion you can rub on that will keep your skin from sagging and wrinkling as you age?

What causes wrinkles? Genes play a role. So does the loss of skin tone that comes with age. Then there's the toll from years of squinting, frowning, and smiling, as well as exposure to the sun.

"We can't control our genes or the natural course of aging, at least not yet," says Sheldon Pinnell, a professor emeritus at the Duke University Medical Center in Durham, North Carolina, where he served 15 years as chair of the division of dermatology. "But we do have some control over our exposure to sunlight, which can damage and age our skin prematurely."

"Photo-aging" is the term for the long-term thinning, sagging, and wrinkling of the skin that's caused by sunlight.

"The difference between skin that's photo-aged and skin that's just plain aged is the difference between the skin on the face or hands and the skin on the buttocks," says Pinnell.

The way photo-aging harms the skin suggests a way to help stave off the damage.

"Sunlight shining on skin creates what we call 'reactive oxygen species,'" explains Pinnell. If they're not neutralized, these high-energy rogue molecules, which include free radicals, can damage the protein structure, cell membranes, and DNA of the skin.

Much of what happens in photoaging is a result of this oxidative stress, says Pinnell. "People, as well as animals and plants, protect themselves from oxidative stress with antioxidants."

The major antioxidants in skin are vitamins C and E, which we get from our diet. Others, like coenzyme Q10, glutathione, and lipoic acid, are made by our bodies, though we can also get them from food. And plants synthesize thousands of antioxidants called polyphenols, which we can absorb from the fruits and vegetables we eat.

"There are multiple antioxidant systems in skin that are working to reduce oxidative stress within cells," explains Barbara Gilchrest, chair of the department of dermatology at Boston University School of Medicine and Boston Medical Center. But that doesn't mean that taking antioxidants will protect your skin.

"Nobody knows whether these systems get overwhelmed during sun exposure, or with the passage of time, or when you smoke a cigarette, or when you eat too much," says Gilchrest. "There's a thought that if you simply had more antioxidants it would be better. That may be true, but it may not."

So far, the research hasn't been promising.

"It's possible to replenish the skin's natural reservoir of antioxidants somewhat with antioxidant supplements," says Pinnell, "but you need very large amounts and you get only a modest effect. The problem is that there are mechanisms in the body that control how much of the antioxidants are absorbed and how much can eventually be delivered to the skin. You can't overcome those mechanisms."

For example, taking daily megadoses of vitamin C (3,000 mg) plus vitamin E (4,400 IU) can boost the skin's defenses modestly, says Pinnell. "But you can't get any more into the skin even if you swallow a carload of the vitamins."

That much vitamin C will give some people diarrhea, and that's twice as much vitamin E as the National Academy of Sciences says is safe to take every day. Too much vitamin E can cause internal bleeding and can hinder blood clotting, at least in animals.

High doses of beta-carotene (at least 40,000 IU a day) also can provide some protection. "But the large amounts necessary may provoke lung cancer in smokers," Pinnell points out.

Researchers haven't looked closely at whether lipoic acid, plant polyphenols, and most other antioxidants found in food can protect human skin.

As for coenzyme Q10: "Taking Co-Q10 to supplement the skin has not been particularly successful," says Valerian Kagan, professor of Environmental and Occupational Health at the University of Pittsburgh. "You can enrich the blood with CoQ10, but the peripheral tissues like skin get almost nothing."

Only one small study has tested a food for its ability to protect the skin. Nine German volunteers were given about 2 1/2 tablespoons of tomato paste every day. After 10 weeks they had 40 percent less reddening of the skin when exposed to ultraviolet (UV) light than ten volunteers who ate no tomato paste. (1) (Eating tomato paste for four weeks provided no protection.) The tomato paste naturally contained 16 milligrams of the carotenoid lycopene.

"This is a significant finding, even though the protection isn't comparable to that of a sunscreen with a high sun protection factor [SPF]," says Judy D. Ribaya-Mercado of the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University in Boston.

"People don't use sunscreen all the time, so substances with sun-protecting properties--presumably lycopene in tomato paste--could provide some degree of protection," she explains. "But the study showed that a person would have to eat lycopene-rich foods for several months before they saw a benefit."

What's more, the trial was too small and short-term to say whether lycopene can protect the skin against long-term skin damage.

"No one has scientifically demonstrated a significant protection or reversal of wrinkling or photo-aging from foods or supplements that contain antioxidants," says Jeffrey Blumberg, Chief of the Antioxidants Research Laboratory at the Human Nutrition Research Center on Aging.

Gimme Some Skin

If you can't eat or take enough antioxidants to protect your skin, how about rubbing them on?

"Applying them directly is one way to solve the problem of getting additional antioxidants into the skin," says Duke University's Sheldon Pinnell. But for that to work, several obstacles have to be overcome.

"Antioxidants are inherently unstable compounds and many of them are deeply colored," Pinnell points out. "That makes them difficult to formulate in an acceptable, stable product for cosmetic use." (Pinnell consults for a Texas "cosmeceuticals" company that markets a vitamin C cream he helped develop.)

What's more, the concentrations of antioxidants need to be substantial, and they have to protect against sunburn, photo-aging, and skin cancer.

"With a combination of topical vitamin C and vitamin E, you can get about a four-fold protection against UV-induced reddening and DNA damage in the skin of pigs," says Pinnell. (Pig skin is virtually identical to human skin.) That's comparable to a weak sunscreen.

"The same protection may occur in humans," he adds. "But, so far, there is very little research to show that."

The bottom line: Research on cosmeceuticals is in its infancy. "I haven't seen any data that establishes the efficacy of topically applied antioxidant preparations, either to reduce oxidative stress or to prevent aging," says Boston University's Barbara Gilchrest.

"Frankly, I don't think anybody really knows to what degree antioxidants get into the skin in an effective form, to what degree the skin's ability to handle oxidative stress is already maxed out, or even which antioxidants would be helpful if delivered in an effective form."

(1) Journal of Nutrition 131: 1449, 2001.

RELATED ARTICLE: Here comes the sun.

"I am completely convinced that sunscreens are helpful in preventing skin cancers and aging of the skin caused by too much sun exposure," says Barbara Gilchrest, chair of the department of dermatology at the Boston University School of Medicine.

"Photons [light particles] are the problem. They're ultimately what causes cancer and damages the skin. And sunscreens absorb or reflect photons. So just on a purely logical basis, they have to help."

Proving that in humans would be difficult, she adds, because skin cancer and photo-aging take decades to develop. "But it's been shown in animal studies that the long-term use of sunscreen definitely reduces cancer and photo-aging."

Sunlight contains two kinds of ultraviolet (UV) light--longer UVA rays and shorter UVB rays.

* UVB is the main cause of sunburns and most skin cancers. It tends to be more intense during the summer, at higher altitudes, and at locations closer to the equator.

* UVA, while not as powerful as UVB, penetrates more deeply into the skin. It's the chief culprit behind wrinkling, leathering, and other forms of photo-aging. It doesn't vary based on season, altitude, or distance from the equator.

New evidence shows that UVA may be more dangerous than researchers thought. According to the Skin Cancer Foundation, "the latest studies show that UVA not only exacerbates UVB's carcinogenic effects, but may directly induce some skin cancers, including melanomas."

A SIMPLE GUIDE TO SUN LOTIONS

* Sunscreens & Sunblocks. Sunscreens chemically absorb harmful ultraviolet rays, while sunblocks physically deflect them. Almost all shield against sunburn-causing UVB (how much protection you get depends on the SPF number). Many also provide some protection against UVA, though there's no way to tell how much (there's no SPF rating for UVA rays). But neither sunscreen nor sunblock is 100 percent effective, so it's important to also protect your skin with hats, sunglasses, clothing, and umbrellas.

* SPF (Sun Protection Factor). It measures how much protection a product provides against sunburn-causing UVB (but not damaging UVA). If you normally get a sunburn after five minutes under the noonday sun, a product with an SPF of 15 would let you stay outside 15 times longer (75 minutes, in this case) before you started to burn. That assumes you've put enough of it on.

* UVA/UVB. Look for a lotion with an SPF of at least 15, which means that it will block or deflect 93 percent of the sun's UVB rays (you can increase the protection to 97 percent with an SPF of 30). Then check the ingredient list to see whether it contains UVA-blockers like avobenzone (also known as Parsol 1789), octylcrylene, benzophenone, zinc oxide (the white paste that lifeguards paint on their noses), or micronized titanium dioxide or clear zinc oxide (which don't leave a greasy white mess). Unfortunately, there's no way to tell how much UVA protection you'll be getting.

* PABA. Some people are sensitive to PABA (para-aminobenzoic acid), a common ingredient in sunscreens. If you break out with an itchy rash, find a sun lotion that's PABA-free (most will say so on the label).

* Applying Sunscreen or Sunblock. Most experts recommend applying a sunscreen or sunblock with an SPF of at least 15 about a half-hour before you go outside, even if it's cloudy (clouds block less than 20 percent of UV radiation). They also say to reapply the lotion every two hours. The American Academy of Dermatology recommends an SPF of at least 30 if you'll be in the sun for more than an hour. If you'll be sweating heavily, you should use an SPF of at least 30 on your face, even if you're going to be outside for less than an hour, since the sweat will rapidly thin it down to a 15 (a waterproof formula will stay on longer when you sweat). If you're at the beach, keep in mind that it takes one ounce--the amount in a shot glass--to adequately cover an average adult's body.

"Unfortunately, most people apply too little sunscreen or sunblock too infrequently to get its full protection," says Duke University's Sheldon Pinnell.

For more information on sunscreen or sunblock, visit www.besunsensible.org, which is maintained by The Sabra Dalby Rightmire Foundation for Melanoma Education and Research as a memorial to a 27-year-old woman who died of melanoma skin cancer in 1999.

RELATED ARTICLE: Ironing out wrinkles.

Here are three of the most popular wrinkle-fighters:

* BOTOX. Last year, the Food and Drug Administration approved injections of Botox, the toxin that causes botulism food poisoning, "to temporarily improve the appearance of moderate to severe frown lines between the eyebrows." It quickly became the fastest-growing cosmetic procedure in the U.S. Injecting Botox into the skin temporarily paralyzes the underlying muscles, which prevents them from contracting and forming frowns. The effect wears off in four to six months.

Some physicians are using Botox to treat facial wrinkles that aren't caused by frowning. "The safety and effectiveness of Botox injections into other regions of the face and neck, alone or in combination with the frown-lines region, have not been clinically evaluated," says the FDA.

* RETINOIC ACID. Retinoic acid, a form of vitamin A that is sold under the brand names Renova, Avita, and Retin-A, can improve fine wrinkles, discoloration, and rough skin from overexposure to sunlight. But it doesn't work for everyone. After applying retinoic acid every day for six months, only a third of users will notice moderate improvement in wrinkles or spotty discoloration. Some over-the-counter anti-wrinkle creams contain the "retinol" form of vitamin A. It's not clear if the skin can convert retinol into enough retinoic acid to have the same benefits as the prescription drug.

* ALPHA HYDROXY ACIDS (AHAs). When rubbed on, they cause the skin to shed its outer layer. According to the FDA, that "supposedly" can reduce wrinkles, spots, and other signs of aging and sun damage (the FDA has never approved AHAs as a drug). Over-the-counter cosmetics typically contain less than one-fifth the concentration of AHAs that are found in the preparations doctors can use. The FDA has proposed an alert for labels of cosmetics that contain AHA. It would warn consumers that the product could increase the skin's sensitivity to sunlight, and would recommend that they use sunscreen and limit sun exposure until at least a week after they stop using the cosmetic.

RELATED ARTICLE: A new wrinkle.

Wrinkle-free for life?

Nicholas Perricone claims that his diet, supplement, and cosmetics regimen prevents--and even reverses--wrinkles, sagging skin, and other signs of aging.

The Connecticut dermatologist seems to be popping up everywhere. His "The Wrinkle Cure" and "The Perricone Prescription" have spent time on the best-seller lists. His expensive line of supplements and even-pricier cosmetics have done well (sales for the cosmetics are expected to top $80 million this year). And his infomercial was one of the top fund-raising attractions for public television stations last year.

One place you won't see him any more is at Yale University. Although the jacket of "The Wrinkle Cure" identifies Perricone as "Yale University's dermatological and anti-aging expert," it turns out that he wasn't exactly teaching or researching up a storm there.

"Dr. Perricone held an unpaid appointment as assistant clinical professor of dermatology at Yale School of Medicine," said a university statement. "In that capacity, he provided oversight to medical students in a clinical setting several times per year. His appointment expired in June 2002."

Perricone quickly landed another academic title, at his alma mater, Michigan State University. Two months after appointing him an adjunct professor, MSU announced that Perricone had given the school $5 million. (The university denies that there was any connection between the appointment and the gift.)

What's so appealing about Perricone's message?

"The smooth skin that contributes so much to your youthful appearance does not have to be lost during mid-life and beyond...." he says in "The Perricone Prescription." "You can reverse and certainly prevent visible skin damage .... Being wrinkle free for life is achievable

But not everyone buys into Perricone's pitch.

"He proclaims these ideas, but he hasn't studied them at all, at least anything that's been published," says Sheldon Pinnell, former chair of the division of dermatology at the Duke University Medical Center. "You can say without any argument at all that Perricone has never done a credible experiment that proves his program does what he says it does."

"There's a retreat from hard data," says Barbara Gilchrest, chair of the department of dermatology at Boston University School of Medicine and Boston Medical Center. "There's lots of testimonials and hand-waving. Nick Perricone has made a fortune talking about this. I'm happy for him, but I'm not sure how much of a service it is to the consuming public."

So why was Perricone's untested program used to raise money by so many public broacasting stations during the past year? "He had good credentials, we didn't hear any criticism of his books, and our producers who watched the program thought it was good," says PBS vice president of programming Gustavo Sagastume. PBS never asked outside experts to review Perricone's claims.

Among those claims (Perricone never responded to our request for an interview):

* PROTEIN. "The contemporary American diet rarely contains protein in sufficient quantity to maintain and repair cell and skin health," says Perricone. That's why he recommends 10 to 14 ounces per day of high-quality animal protein like fish, egg whites, or skinless chicken and turkey breast.

The truth: Most Americans already eat about twice as much protein as they need, much of it high-quality animal protein. And no one has tested a high-protein diet on skin wrinkling.

* GLYCEMIC HORRORS. "Think twice before you reach for a carrot," says Perricone. Why? "When foods rapidly convert to sugar in the bloodstream ... they cause browning, or glycating of the protein in your tissues. ... Glycation can occur in skin as well, creating detrimental age-related changes to collagen--and that means deep wrinkles." Among Perricone's "Foods to Avoid": bananas, bread, cereals (except non-instant oatmeal), dried fruit, fruit juice, mango, oranges, papaya, popcorn, rice, and watermelon. Vegetables to shun include beets, corn, cooked carrots, and sweet potatoes.

The truth: "There are several missing links of scientific data that would be required to substantiate this claim," says blood sugar (glucose) expert Cyril Kendall of the University of Toronto. "As far as I am aware, no studies have looked at glucose in the diet and skin wrinkling. The claim just isn't supported by the scientific literature."

* SALMON. "Of all the foods that can keep you young," says Perricone, "fish tops the list." He singles out salmon, because of its protein, anti-inflammatory fatty acids, and (he claims) DMAE (dimethylaminoethanol). He calls the fish "your magic bullet for great skin tone, keeping your face firm and contoured."

The truth: While salmon and other fish may reduce your risk of heart disease, there is no evidence that they prevent wrinkles. What's more, there is no credible evidence that DMAE in food or supplements can smooth the skin. And none of the scientists we contacted (at the National Marine Fisheries Service, the U.S. Department of Agriculture, and the School of Aquatic and Fishery Science at the University of Washington) could even confirm that DMAE is found in salmon.

* ALPHA LIPOIC ACID. It's "one of the most powerful antiaging, antioxidant, anti-inflammatories available," says Perricone. "It blocks the production of enzymes that damage the collagen fibers, preserving a smooth skin surface. It is equally effective in preventing glycation, the harmful effects of sugar molecules on collagen fibers."

The truth: "Lipoic acid is an antioxidant and does have antioxidant powers," says Pinnell. "But there's no evidence that having extra lipoic acid in the skin is effective. It's not a bad idea. It just doesn't seem to work."

Then there's Perricone's daily vitamin regimen--a multivitamin and at least a dozen other supplements with breakfast and half a dozen more with lunch. You can conveniently order them from Perricone's Web site. Total cost for the "antioxidants, B-complex energy enhancers, macrominerals, lipotropic factors, enzymes, and herbal extracts" in Perricone's Skin & Total Body Nutritional Supplements: $120 a month. (You can also order a month's worth of Perricone's Weight Management Program supplements for $195, but that's another story.)

And don't forget the liquid cleansers, moisturizers, and morning and bedtime wrinkle-free skin care products you'll need. Perricone offers four "recommended" collections of "cosmeceuticals." Recommendation #3, for example, consists of "8 products designed to reduce the appearance of loss of tone, sagging skin, and fine lines." At $438, it's the least costly of the four.

Being wrinkle-free for life isn't cheap.