Copyright © 2007 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 12, Number 3 September 2007 Alternative Medicine Review Volume 12, Number 3 2007 Review Article Page 246 Abstract Frailty syndrome (FS) has become increasingly recognized as a major predictor of co-morbidities and mortality in older individuals. Interventions with the potential to benefit frail elders include nutritional supplementation (vitamins D, carotenoids, creatine, dehydroepiandrosterone (DHEA), and beta-hydroxy- beta-methylbutyrate) and exercise modalities (tai chi and cobblestone walking). While these have not been explicitly tested for their impact on FS, vitamin D supplementation appears to offer significant promise in enhancing long-term health of the elderly. Exercise modalities such as tai chi and cobblestone walking, because of probable low risk and ease of participation, may also confer benefit. Additional studies are needed to investigate interventions that directly prevent, delay, and/or ameliorate frailty. Successful therapies may well involve multi-component approaches utilizing a combination of medication, nutritional supplementation, and exercise. (Altern Med Rev 2007;12(3):246-258) Introduction Frailty syndrome (FS) has become increas- ingly recognized as a major concern for older individu- als. While deinitions of FS vary, most experts agree this syndrome is characterized by a reduced functional reserve and impaired adaptive capacity resulting from cumulative decline of multiple subsystems, and causes increased vulnerability leading to adverse outcomes. he most widely accepted criteria are those of Fried et al, who deine FS as including three or more of the following: weakness, slow walking speed, self-reported exhaustion, low physical activity, and unintentional weight loss (Table 1). 1 A large survey of over 5,000 E. Paul Cherniack, MD; Hermes J. Florez, MD, PhD; Bruce R. Troen, MD Emerging herapies to Treat Frailty Syndrome in the Elderly E. Paul Cherniack, MD – Division of Geriatrics and Gerontology, Miller School of Medicine, University of Miami and the Miami VA Health Care System. Correspondence address: Room 1D200, Miami VA Medical Center, 1201 NW 16 St, Miami, FL 33125 Email: evan.cherniack@med.va.gov Hermes Florez, MD – Division of Geriatrics and Gerontology, Miller School of Medicine, University of Miami and the Miami VA Health Care System; Division of Endocrinology, Miller School of Medicine, University of Miami and the Miami VA Health Care System. Bruce R. Troen, MD – Division of Geriatrics and Gerontology, Miller School of Medicine, University of Miami and the Miami VA Health Care System. community-dwelling elderly, the Cardiovascular Health Study, determined that seven percent of those over age 65 and 30 percent of those ≥80 years demonstrate diag- nostic criteria compatible with FS. he presence of FS is a predictor for hospitalization, disability, decreasing mobility, falls, and even death. Women are frailer than men, and the risk of death from frailty is independent of the presence of chronic disease. 2 Pathophysiology and Risk Factors for FS FS is believed to be the result of multiple path- ological processes common among the elderly. 3 Aging induces changes in hormone cascades (menopause, an- dropause, somatopause, and adrenopause) and the im- mune system, modulating their eiciency and efective- ness in determining a response to stressors. Nutritional Risk Factors Several large epidemiological trials have eluci- dated potential nutritional risk factors. he Women’s Health and Aging Studies I and II (WHAS) utilized the deinition by Fried et al in identifying risk factors for FS in a cohort of 1,002 women in the Baltimore area in 1992. 4,5 Women with serum carotenoids (representative of intake of fruits and vegetables) in the lowest quartile (adjusted for age, smoking status, and chronic pulmo- nary disease) were at a slightly greater risk for frailty than