Copyright © 2008 John Wiley & Sons, Ltd. Phytother. Res. 22, 1292–1298 (2008) DOI: 10.1002/ptr 1292 J. A. OLALDE ET AL. Copyright © 2008 John Wiley & Sons, Ltd. PHYTOTHERAPY RESEARCH Phytother. Res. 22, 1292–1298 (2008) Published online 20 June 2008 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/ptr.2482 Clinical Outcomes of Diabetic Foot Management with Circulat J. A. Olalde, M. Magarici, F. Amendola, O. del Castillo*, S. Gonzalez and A. Muhammad Adaptogenic Medical Center, Caracas 1080, Venezuela Major and minor lower-extremity amputation is a common complication among diabetics. Various sources indicate diabetic foot ulcer prevalence at between 2.2% and 15% in diabetics. This study evaluates the efficacy and tolerance of a standardized plant extract combination, Circulat, developed for the prevention and treatment of severe manifestations of type 2 diabetes, such as necrotic damage of the foot. Thus, a retrospective cohort study was carried out in 174 patients treated with Circulat with diabetic foot grades D1–D3, according to The University of Texas Wound Classification System, in 50 medical centers, from 2004 to 2007. Circulat obtained 50.57% complete cure of diabetic foot, significant improvement in 37.9% and prevented amputation in 88.5% of the study’s total population. The treatment was well tolerated. Four patients (2.3%) had slight gastrointestinal unrest which did not warrant suspension of treatment. Copyright © 2008 John Wiley & Sons, Ltd. Keywords: diabetes; diabetic foot amputation; adaptogens; systemic. Received 15 June 2007 Revised 8 October 2007 Accepted 12 November 2007 * Correspondence to: O. del Castillo, Adaptogenic Medical Center, Calle Luis de Camoens c/c Del Arenal, La Trinidad, Caracas 1080, Venezuela. E-mail: corpgov2004@yahoo.com INTRODUCTION The World Health Organization (WHO, 2006) estimates that more than 180 million people worldwide have dia- betes. This number is likely to more than double by 2030. Diabetic foot ulcers are one of the most frequent complications of this disease. The prevalence of diabetic foot ulcers has been estimated at 2.2% to 15% (Abbot et al., 2002; Gulam-Abbas et al., 2002). The difference being attributed to the diversity of risk factors, ethnicity, age, sex, level of education, quality of health service and others (Table 1). Diabetic foot ulcers represent a large emotional and economic burden on patients and caregivers as well. Foot complications are caused by diabetic neuropathy or peripheral ischemic vessel dis- ease or a combination of both (Ratzmann et al., 1994) and are the most frequent reason for hospitalization in patients with diabetes. Diabetic foot complications are the most common cause of non-traumatic lower extremity amputations in the industrialized world. The risk of lower extremity amputation is 15–46 times higher in diabetics than in persons who do not have diabetes mellitus (Nabuura-Franssen et al., 2005; Armstrong et al., 1997). Approximately 40–60% of all lower extremity amputations are performed in patients with diabetes. More than 85% of these amputations are precipitated by a foot ulcer deteriorating to deep infection or gangrene (Apelqvist and Larsson, 2000). In people with healed diabetic foot ulcers, the 5 year cumulative rate of ulcer recurrence is 66% and of amputation is 12% (Apelqvist et al., 1993). The high amputation incidence and healing failure after lower extremity amputation for the treatment of diabetic foot ulcer (Malay et al., 2006) is a distinct signal that the efficiency of conven- tional medical treatments used is less than optimal. This substantiates the need to search for effective therapeu- tic alternatives and to diminish the suffering and high economic and social costs caused by this common dia- betic patient complication. Various medicinal plants have been used traditionally for the treatment of circu- latory obstructive diseases. In the last couple of decades many of their active principles and action mechanisms have been discovered. Also, traditional healing know- how has been proven to be effective in many cases. This raises the possibility of using herbal therapeutic protocols to complement conventional treatments for complications in diabetes. In particular, there is mount- ing evidence which demonstrates that medicinal plants contain synergistic and/or side-effect neutralizing com- binations (Thyagarajan et al., 2007; Gilani and Rahman, 2005). In contrast to synthetic pharmaceuticals based upon single chemicals, many phytomedicines exert their beneficial effects through the additive or synergistic action of their multitude of constituents acting at single or multiple target sites (Dalby-Brown et al., 2005); because of their primary and secondary metabolite roles (Greenspan et al., 1994) and the adjuvant substances which enhance the activity of components actually responsible for the effect (Gilbert and Alves, 2003; Stermitz et al., 2000). In order to take maximum advan- tage of the therapeutic properties as well as benefits of the synergistic action of the active principles in medi- cinal plants, it is necessary to use herbal combinations. Herbal formulations have been used for hundreds of years, however, little is known of the methodology to combine plants and obtain effective compositions. The Systemic Theory provided the fundamentals which allowed the formulation of an effective herbal composition, Circulat, patent application number 11/ 271,940, for treating diabetic foot (Olalde, 2005a, b and c; Olalde et al., 2005). Circulat is a systemic standardized plant extract combination consisting of (1) Energy plants (E) associated with ATP synthesis (such as tricarboxylic