A Skeptical View of the Perricone Prescription

Harriet Hall, M.D.
Stephen Barrett, M.D.

Nicholas Perricone, M.D., has written three similar books: The Wrinkle Cure [1], The Perricone Prescription [2]; and The Acne Prescription [3]. All contain many claims that are questionable, controversial, fanciful, unsupported by published evidence, or just plain wrong. Although he mentions standard skin-care treatments, sometimes favorably, his books provide little guidance about when they might be appropriate or sufficient. Although he provides long lists of references, practically none of them directly support what he promises. Despite this, his books have made best seller lists and the Public Broadcasting System (PBS) has featured him during fundraising campaigns.

Perricone claims that following his advice can quickly improve appearance, improve general health, increase mental sharpness, and make people more energetic. In The Perricone Prescription, for example, he promises to “stop skin from wrinkling, sagging and dulling” and says that, “being wrinkle free for life is achievable” if you follow his 28-day program. He offers “increased vitality, sharpened cognitive and problem-solving skills, and improved memory” and claims that “looking and feeling old is now an option.” He also describes his program as “proven . . . to reverse the many signs of premature aging and stop its progress.” [2:1-5]

Background History

Dr. Perricone makes much of his connection with Yale University. He is a former assistant clinical professor of dermatology at Yale University School of Medicine—an unpaid position in which he supervised students from time to time. However, his affiliation ended in 2002 when his contract was not renewed. In an interview reported in the Washington Post, Perricone said that the school authorities had been very critical of his books, public appearances, and anti-inflammation theories [4]. The report also noted that he subsequently became an adjunct (visiting) professor at Michigan State University’s College of Human Medicine and pledged $5 million to establish the Perricone Division of Dermatology there.

Perricone’s books are sprinkled with statements that his ideas are based on his own research. However, the extent and quality of this research is unclear. A PubMed search for his name brought up only six citations, of which only two appear to be original research, both on topical glycolic acid [5,6]. His books describe situations in which he tested various ideas in a few patients, usually over a short period of time, but he provides few details and apparently published none of those findings in medical journals.

Most of Perricone’s recommended strategies are nutrition-related. In The Wrinkle Cure, he describes how his interest in this subject developed:

My own fascination with nutrition was sparked during my undergraduate days, before I entered medical school. I had always suffered from sallow, acne-plagued skin, allergies, and fatigue, so I started reading everything I could find on the subject—which, at the time, meant pretty much everything written by Linus Pauling, Ph.D. . . . and Adelle Davis. I began experimenting with vitamins on my own, and the results were gratifying. My skin and allergies improved, and I had much more energy. . . .

When I entered medical school, however, my interest in nutrition made me an eccentric. My classmates thought I was nuts because I popped vitamins after meals and bundled up to go running in the dark, cold mornings of Michigan winters. [1:3,6].

The references to Pauling and Davis may help explain why Perricone spouts so many strange ideas. Although Pauling was a great chemist, his late-in-life beliefs in vitamin megadoses have been thoroughly discredited [7]. Adelle Davis achieved great popularity during the 1970s, but close examination of her writings indicates that she consistently misinterpreted research reports or simply made things up [8]. The irrational nutrition-related beliefs Perricone absorbed before going to medical school were apparently untouched by his science-based education.

Perricone’s “Prescription”

The Perricone Prescription provides detailed instructions that include exactly what foods to eat, when and in what order to eat them (proteins first), what exercises to do, what supplements to take with each meal, and what to apply to your skin at what times of day. He even includes a section of recommended recipes. His program includes:

• Diet: Three meals and two snacks daily, high quality protein (above all, wild salmon), “good” fats, and carbohydrates with a low glycemic index. No sugar. A long list of prohibited foods including carrots, bananas, duck, potatoes, flour, raisins, corn, soda (even diet soda) and many others.
• Nutrient supplements: 25 different ones, some taken more than once a day: alpha lipoic acid, vitamins A, B1, B2, B3, B5, B6, B12, folate, biotin, vitamin C, vitamin C ester, vitamin E, calcium, chromium, magnesium, selenium, l-carnitine, acetyl l-carnitine, coenzyme Q10, l-glutamine, omega-3 fatty acids, grape seed extract, gamma linoleic acid, and turmeric.
• Skin treatments: sunscreens, cleansers, moisturizers, eye-care products and enriched night cream; various creams with ingredients such as vitamin C, vitamin C ester, alpha lipoic acid, DMAE, PPC, tocotrienol, and olive oil.
• Exercise: For strength, endurance, and flexibility; 40 minutes a day, 6 days a week.
• Miscellaneous advice: 8-10 glasses of spring water a day; no tobacco, coffee, or alcohol (but tea is allowed); melatonin for sleep if needed.

Perricone markets his own line of high-priced nutritional supplements and skin care products worldwide. Typical prices from his Web site include:

$120 for 4 oz alpha lipoic acid and other ingredients for spider veins

$570 for 2 oz neuropeptide facial conformer

$195 for a 30-day supply of supplements for weight loss

$438-458 monthly for the entire skin and nutrient program based on skin type [9].

In November 2003, The Wall Street Journal reported that Perricone’s company (N.V. Perricone) grossed $11.9 million in 2001, $42.4 million in 2002, and was expected to top $52 million in 2003 [10]. The article also noted that Perricone’s PBS fundraising specials had generated over $4 million for PBS in both 2001 and 2002.

Questionable, Unverifiable, and Erroneous Statements

Perricone says that he gradually came to believe inflammation is the underlying cause of aging and of many diseases and that his own research shows that treating inflammation would reverse the aging process. In fact, he characterizes inflammation as “the key to the whole process of disease of every type.” [2:20] Inflammation is indeed associated with many diseases, but it is not always clear whether the inflammation is a cause or a result. Nor is it clear that nutrients that help fight inflammation (such as vitamins C and E) do anything to reverse most of those diseases. Inflammation is characterized by the presence of white blood cells in a skin biopsy specimen. However, their presence can be due to hundreds of different causes, including systemic diseases, infections, foreign substances, insect bites, autoimmune processes, viruses, genetic abnormalities, and malignancies. Inflammation can be nonspecific and even be due to scratching. And the presence of white cells doesn’t necessarily mean there are any associated clinical or molecular abnormalities [11]. Inflammation doesn’t always increase with age; the inflammatory response to skin injuries actually decreases as you get older [12].

Dietary deficiencies can cause inflammation in the skin (pellagra is a classic example), but there’s no evidence that supplementing an already adequate diet would prevent inflammation. Nor is there evidence that inflammation causes wrinkles. (The leading controllable factors are sun damage and cigarette smoking.) If Perricone truly wanted to test his theories, it would not be difficult. They could be tested on an animal model with biopsies before and after various treatments. Also, one could look for epidemiologic data on patients taking prednisone or nonsterioidal antiinflammatory drugs (NSAIDS) to see whether they have fewer wrinkles [13].

In acne, hair follicles become plugged with comedos composed of dead skin cells and sebum (a mixture of fats and waxes). If bacteria invade, the surrounding skin can become inflamed, and pimples or pustules may form. Most people with acne have a mild (noninflammatory) form and get occasional whiteheads or blackheads. There is little evidence that acne is related to diet. If self-experimentation suggests that a specific food aggravates acne, avoiding the food may be reasonable, but Perricone’s sweeping claims have no scientific support.

Page 33 of The Perricone Prescription illustrates an extraordinary degree of illogical thinking about nutrition. After describing a breakfast consisting of orange juice, cold cereal with banana, skim milk, a low-fat bran muffin, margarine and coffee, the book states:

As [Megan] drinks the juice, she is causing a burst of inflammation in her body as the juice floods her bloodstream with sugar. This causes a sharp spike in her insulin levels, resulting in a rapid acceleration of the aging process, increasing the risk of heart disease, every form of cancer, memory loss, and mental deterioration. To add to the problems, the sugar flood is causing the collagen to cross-link, laying the foundation for the birth of wrinkles, sagging, and loss of tone.

Page 45 contains an equally ridiculous passage which concludes that eating bagels, cookies, or caffeinated, sugary sodas—which Perricone inappropriately regards as addicting—places people at risk for “exhausting our pancreas, burning out our adrenals, and placing us at risk for insulin resistance and diabetes.”

Here are more of Perricone’s claims followed by our comments in brackets:

• Substances like olive oil “penetrate, strengthen, and refresh your skin cells.” [What do “strengthening” and “refreshing “your skin cells mean?]
• You look puffy the morning after eating Chinese food because of an inflammatory response to what you ate. [Any puffiness would probably be because the salt and MSG caused the body to temporarily retain water.]
• When you are mildly dehydrated your metabolism drops and you gain weight. [Actually, dehydration usually decreases appetite and results in weight loss.]
• His program works by a synergy between diet, supplements, skin care, and exercise. [Synergy means the combination works better than the sum of the individual components. There are no published data comparing the combination with each factor alone or with other combinations.]
• Slow, steady release of insulin into our bloodstream keeps us younger. [He doesn’t indicate how he thinks this could be measured. It can’t.]
• Sugar makes the insulin receptors on the cells burn out. [Untrue]
• The contemporary American diet rarely contains enough protein. [Untrue. Americans tend to consume more protein than they need.]
• DMAE is your magic bullet for great skin tone. [A PubMed search shows only one small study that showed an effect of topical DMAE on skin [14]]
• There are probably unidentified components of salmon that promote health and slow aging. [This possible, but he has no basis for saying it is probable.]
• Salmon improves manic-depressive patients who don’t respond to medication. [He mentions a study but doesn’t give a citation for it, and it is not listed in PubMed.]
• Socrates prescribed olive oil for various diseases. [So what?]
• Olive trees live for centuries and re-grow after being cut to the ground. [Implied benefits from olive oil for human longevity by magical analogy.]
• Adults should limit milk intake because they may have lactose intolerance or allergies. [It would make far more sense to base an individual decision on whether the individual actually is intolerant.]
• Alcohol is bad, so hard liquor is bad, but wine is OK. [A glass of wine and a shot of whiskey contain approximately the same amount of alcohol.]
• Avoid tap water; drink spring water. [Bottled water is not tested as thoroughly as public water supplies and many brands fail to meet tap water standards. Several surveys have found more contaminants, bacteria, etc. in some bottled waters than in tap water. Tap water is generally safer.]
• Spring water flushes toxins from the body. [What toxins? What difference does it make whether it’s spring water or other fluids?]
• Everyone needs 8-10 glasses of water a day. [A comparison of two diets, one with and one without plain water, showed no difference in hydration whether water was supplied by plain water or other beverages [15]].
• The same substances work on the central nervous system and the skin. [A personal observation, not otherwise supported. He theorizes that the nervous stem and skin are alike because they originated in the same one of three cell layers of the early embryo.]
• Vitamin C deficiency causes wrinkles. [Sun exposure and tobacco use are the only recognized factors known to cause wrinkles.]
• Growth hormone is the true “youth hormone.” [Only in the sense that it helps youths grow into adults!]
• Coffee causes weight gain, while tea cause weight loss. [Neither is correct.]
• Lack of essential fatty acids can cause miscarriage. [A PubMed search for fatty acids and miscarriage showed only one study in the blue fox; it showed just the opposite—that supplementing the diet with essential fatty acids in the form of evening primrose oil increased the rate of miscarriage.]
• Alpha-lipoic acid is an anti-aging drug. [There are no known anti-aging drugs.]

Lack of Science

Dr. Perricone would be more credible if he could show us a study demonstrating that people who followed his prescription lived longer, had “younger” skin demonstrated by objective measures, or felt better compared to those on a placebo program—or that they were better in any measurable way. Instead, he provides only testimonials, exaggerated claims, partial truths, and incorrect statements. He cherry-picks possibly supportive studies from the literature and ignores contradictory studies. He cites lots of lab studies (in vitro or in animals), but few that demonstrate any clinical effects in humans. The diet he recommends is low in calories, and weight loss alone may improve the way his patients look and feel. His advice about tobacco and sunscreens is appropriate, but there is little science behind the rest of his program. He seems to have gathered every nutrient and skin cream he had any reason to hypothesize might work and advised using all of them. A more rational approach would have been to first see which ones really worked, and later to see if any combinations of the effective agents worked better than a single agent. No scientist worth his salt does experiments without controls; Perricone treats everyone, so that there is no basis for comparison.

The Perricone Prescription includes full-color before-and-after photographs of women who tried its 28-day program. These photos are far from convincing, with differences in position, lighting, facial expression, makeup, and weight loss that could affect the appearance. The reader is asked to make purely subjective judgments and to notice undefined qualities such as “vibrancy,” “radiance,” and “improved contours.” Dr. Hall’s own informal poll indicated that most people prefer some of the “befores” to the “afters.”

A Washington Post reporter’s experience illustrates how inexact this type of study can be. Page 12 of The Perricone Prescription states that, “Without exception, every patient who has tried the Three-Day Nutritional Face-lift has had good results, and has returned convinced that my Wrinkle-Free Program works. And you will, too.” Noting that this statement is preposterous, the reporter decided to test the program on herself. On the fourth day, she had lost three pounds, and it seemed to her that her pores were smaller, her eyelids less heavy and her chin line “less blurry.” However, 18 out of 26 of her friends who looked at before-and-after photographs said she looked younger before she started the program [4].

Perricone and his patients may agree that they look better after treatment, but the photographs are the only attempt he makes to present objective evidence. It seems rather silly to depend on subjective impressions and photographs when several objective methods of measuring improvement are available. Reputable published skin studies have used skin surface measurements by semi-automated computer morphometry, laser profilometry, and skin biopsies whose specimens are examined with immunohistochemistry and electron microscopy [16]. Moreover, the creams and lotions he recommends could easily have been evaluated by applying them to one side of the face and using the other side as a control.

Perricone provides little information from sources that disagree with him. Mercury in fish is a possible concern with a high salmon diet, but he doesn’t even mention it. He lists all the positive effects of nutrients but omits to mention the toxic effects of high doses, even though some of his supplements may push people into the toxic range. He does not mention that only three nutritional factors have ever been found to correlate with longer life in mammals: calorie restriction, and restriction of methionine and tryptophan—in rodents [17].

Overview

Dr. Perricone has mixed a pinch of science with a gallon of imagination to create an elaborate, time-consuming, expensive, prescription for a healthy life and younger skin. There is no reason to think his program is more effective than standard measures. Although some of his advice is standard, most of his recommendations are based on speculation and fanciful interpretation of selected medical literature. He makes lots of money by convincing patients and consumers, but he hasn’t succeeded in convincing critical thinkers, doctors, scientists, or anyone who wants to see hard evidence. Perricone’s “prescription” isn’t science; it’s creative salesmanship.

For Additional Information

• Paula Begoun’s Product Review

References

1. Perricone N. The Wrinkle Cure: Unlock the Power of Cosmeceuticals for Supple, Youthful Skin. New York: Warner Books, 2000.
2. Perricone N. The Perricone Prescription: A Physician’s 28-Day Program for Total Body and Face Rejuvenation. New York: HarperCollins, 2002.
3. Perricone N. The Acne Prescription: The Perricone Program for Clear and Healthy Skin at Any Age. New York: HarperCollins, 2003.
4. Weiss S. Got wrinkles? Go fish. Washington Post, Dec 17, 2002.
5. Perricone NV, DiNardo JC. Photoprotective and antiinflammatory effects of topical glycolic acid. Dermatologic Surgery 22:435-437, 1996.
6. Perricone NV. Treatment of pseudofolliculitis barbae with topical glycolic acid: a report of two studies. Cutis 52:232-235, 1993.
7. Barrett S. The dark side of Linus Pauling’s legacy. Quackwatch Web site, May 5, 2001.
8. Barrett S. Adelle Davis’s legacy. Quackwatch, March 27, 1999.
9. Supplements. N.V. Perricone, M.D., Cosmeceuticals, accessed Feb 27, 2004.
10. Beatty S. Hot at the mall: Skin-care products from physicians. The Wall Street Journal, Nov 14, 2003, pp A1, A8.
11. Bosset S and others. Photoageing shows histological features of chronic skin inflammation without clinical and molecular abnormalities. British Journal of Dermatology 149:826-835, 2003.
12. Swift ME, et al. Age-related alterations in the inflammatory response to dermal injury. Journal of Investigative Dermatology 117:1027-1035, 2001.
13. Bredt R. Personal communication to Harriet Hall. M.D., Feb 6, 2004.
14. Uhoda I and others. Split face study on the cutaneous tensile effect of 2-dimethylaminoethanol (deanol) gel. Skin Research and Technology 8:164-167, 2002.
15. Grandjean AC and others. The effect on hydration of two diets, one with and one without plain water. Journal of the American College of Nutrition 22:165-173, 2003.
16. Beitner H. Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoageing of facial skin. British Journal of Dermatology 149:841-849, 2003.
17. Zimmerman JA and others. Nutritional control of aging. Experimental Gerontolology Jan-Feb;38(1-2):47-52, 2003.

This article was originally published in Quackwatch