The ‘Fountain of Youth’ is as elusive now as it was for de Leon

by Anthony M. DiGioia III, MD; and John M. Tokish, MD

The search for the so-called “Fountain of Youth” is at least as alive today as it was in 1513, when Ponce de Leon first explored Florida in search of a remedy for aging. But while de Leon never found such a remedy, the American baby boomer has championed his cause. This segment of the population — born between 1946 and 1964 — numbers 76 million, and will spend more than $72 billion dollars on products and services to slow the aging process in 2009 alone.

There is considerable controversy, however, as to the safety and efficacy of these age-defying products. Many are not controlled by the FDA, and therefore little oversight is in place to ensure safety and efficacy.

There are several drugs and supplements that are in popular use by anti-aging clinics around the country. Some are actually well studied for use in an aging population, but as has been the case since ancient times, there is no shortage of snake-oil salesmen in the marketplace.

Testosterone

Perhaps the “gold standard” performance enhancement drug is testosterone. First synthesized in 1935, its use to treat various medical conditions has skyrocketed. Since 1993, testosterone prescriptions have increased at an annual rate of 25% to 30%, and overall there has been a 500% increase in prescription use throughout the last decade.

Anthony M. DiGioia III

It is well known that testosterone levels in males decrease with age. Around 20% of 60 year olds, and 50% of 80 year olds exhibit total serum testosterone levels below the normal range for young men. Such low levels are commonly associated with erectile dysfunction, loss of libido, muscle weakness, lower bone mass, and frailty.

Several meta-analyses and systematic reviews establish a consensus that testosterone supplementation has positive effects on body composition, muscle strength, bone density, sexual function, and depression. Most interesting to the orthopedic surgeon, testosterone supplementation may help reduce fall risk and increase independence after hospitalization. One wonders if there may be a role for using this powerful drug in the perioperative setting after hip fracture, joint replacement or other major surgery. While the side effects of testosterone supplementation are well documented in abuse cases, most studies show that at doses used, there are few side effects associated with its use in an aging population.

Human growth hormone (hGH)

The “birth” of hGH as an anti-aging treatment likely occurred in 1990 when a study was published reporting that a short course of hGH therapy could reverse decades of age-related changes in body composition in otherwise healthy elderly men. Since then, the popularity of hGH therapy has experienced exponential growth and has become a noted drug of abuse in movie stars, professional athletes and laymen alike. One study estimated that 30,000 people used the drug for anti-aging purposes in 2004, a tenfold increase since the mid -1990s, and annual sales of hGH worldwide exceed $1.5 billion. Notwithstanding this popularity, the scientific community continues to be reticent of hGH as an anti-aging treatment. The American Association of Clinical Endocrinologists has adopted a position statement against its use, and the distribution of hGH for use as an anti-aging therapy in the United States is illegal.

Several studies have investigated hGH in aging populations. An overall review reports modest increases in muscle volume (7%), but with no improvement in any measure of muscle strength. This lack of any benefit to muscle strength has been confirmed in several other trials, making the scientific literature somewhat unanimous in its lack of positive effect on muscle.

Numerous side effects have been associated with hGH use, including an increase in soft tissue edema, carpal tunnel syndrome, arthralgias, gynecomastia, and even new onset diabetes mellitus.

In conclusion, while hGH continues to experience a major cult following for its anti-aging effects, there is good science to support that it is nearly worthless as a performance enhancer.

Resveratrol

Perhaps the most recent promising supplement with anti-aging applications is resveratrol, a phytolexin found in red wine and other plant derived products. Resveratrol garnered international attention after a 2003 study showed it to significantly extend the life span in yeast, through a similar mechanism to severe caloric restriction. Subsequent studies repeated this life extension property in other species.

Mice on a high-fat diet supplemented with resveratrol, may have a 30% lower risk of death than mice on a high-fat diet alone, and have better running performance. This has spurned a venture capital explosion, and several pharmaceutical products are currently under development to exploit these early results. Studies like these make resveratrol a promising potential for age-related decline. It is the first supplement to hold the promise of life extension itself, though there is a wide chasm between the current science, and a claim that this product is the fountain of youth.

Antioxidants

Antioxidants are molecules capable of preventing oxidation in cells. Oxidation reactions can produce free radicals which start chain reactions that can damage cells. Antioxidants can reduce these chains and prevent this damage. Many diseases are thought to be associated with oxidative stress, such as Alzheimer’s disease, diabetes, rheumatoid arthritis, and heart disease. Common antioxidants include vitamins C and E, glutathione, melatonin, and carotenes.

While supplementation with anti-oxidants have been attempted to treat chronic diseases such as cancer and heart disease, it has not yet been shown effective. In fact, high-dose antioxidant therapy has actually been shown to increase mortality. It should be understood, however, that the mechanisms of these disease processes are quite complex and multifactorial, and antioxidant treatment may yet prove to be an effective tool in disease prevention and treatment. Supraphysiologic supplementation at this time, however, can not be recommended.

Still elusive

The fountain of youth remains an elusive search, though scientists are beginning to understand the complex causes of aging. Unfortunately, the marketing of the fountain has drastically outpaced its science. Nevertheless, strategies to both extend the length and quality of life receive more scientific attention now than ever before, and progress is being made. As clinicians, we should balance an open mind for potential anti-aging applications, with a healthy skepticism for snake oil.

In the coming years, it may be that hormone replacement therapy becomes part of a comprehensive perioperative plan, perhaps allowing earlier independence, faster return of strength, and improved overall outcomes, but the science must hurry to catch up to the marketing.

References:

• Selling the Promise of Youth. Business Week. March 20, 2006.

• Anthony M. DiGioia III, MD, can be reached at Renaissance Orthopaedics, PC, and Pittsburgh, Pennsylvania Innovation Center, Magee-Womens Hospital of UPMC, Pittsburgh, Pennsylvania. He is a shareholder in Blue Belt Technologies.