in developing countries , botanical dietary 
 supplements and traditional medicines are often the primary sources 
 of health care for disease prevention and treatment . in the united states where 20% of adults report using botanical 
 dietary supplements and to a smaller extent 
 in europe , these products are used primarily for health maintenance . 
 in 2010 , the worldwide market for botanical dietary supplements was 
 reported to be $ 33 billion . since enactment 
 of the united states dietary supplement and health education act of 
 1994 , which exempted dietary supplements from regulation as drugs 
 or foods , the use of these products has grown steadily in the united 
 states , reaching over $ 6 billion usd in 
 2013 . although worldwide use of 
 botanical dietary supplements increased steadily during the past 2 
 decades , regulation varies considerably but in most markets requires at least botanical authentication and 
 quality control . in the united states , botanical dietary supplements 
 do not require proof of efficacy and do not require premarketing approval 
 by the u.s . food and drug administration ( fda ) , unless druglike efficacy 
 is claimed . furthermore , the safety of botanical dietary supplements 
 remains the responsibility of the manufacturer , and safety assurance 
 is limited to postmarketing surveillance for adverse effects . in europe , if therapeutic claims are made , then the european 
 union requires evidence of safety and efficacy for botanical dietary 
 supplements , unless they are mixtures of botanicals with a long history 
 of human use , in which case they are termed  traditional herbal 
 medicinal products  and are subject only to safety and quality 
 requirements as in the united states . however , 
 when botanical dietary supplements are marketed for health maintenance 
 or promotion , then the eu regulates them as food supplements , and 
 evidence of efficacy must be provided if health claims are made . in response to concerns regarding botanical 
 integrity and quality assurance , the 
 u.s . fda recently instituted the requirement that botanical dietary 
 supplements under its jurisdiction be prepared using good manufacturing 
 practice ( gmp ) . federal 
 trade commission and are similar to those 
 in effect in the eu . enforcement of these regulations is helping to 
 ensure that consumers are able to purchase accurately labeled botanical 
 dietary supplements that are not contaminated with heavy metals , pesticides , 
 herbicides , or microbes . however , these regulations do not require 
 testing of botanical dietary supplements for potential adverse interactions 
 with prescription medicines nor do they require evidence of efficacy . consumers of botanical dietary supplements expect a consistent 
 and safe product , and current labeling guidelines and gmp requirements 
 in major markets are helping to achieve these objectives . however , 
 safety issues such as possible drug  botanical interactions 
 remain unaddressed for most botanicals , and few rigorously designed 
 clinical trials have shown efficacy . since being established in 1999 , 
 the uic botanical center for dietary supplements research has promoted 
 a set of best practices for the reproducible production and evaluation 
 of the safety and efficacy of botanical dietary supplements ( figure 1 ) . in this review , an updated version of these best practices is described that may be 
 followed stepwise to ensure , first of all , that research on botanical 
 dietary supplements is scientifically sound and reproducible and , 
 second , that a botanical dietary supplement can be produced that has 
 defined safety and efficacy . steps for the development , evaluation , and production 
 of safe , reproducible , and effective botanical dietary supplements . as the worldwide 
 use of botanical dietary supplements continues to grow , the need for 
 scientific evaluation of the safety and efficacy of these products 
 is becoming ever greater . the same rigorous preclinical and clinical 
 approaches used to discover and develop drugs may be applied ( with 
 minor adjustments ) to the investigation of botanical dietary supplements 
 using a stepwise approach as outlined in this review . among these 
 steps , the requirement that gmp be used in the preparation of these 
 products has contributed significantly to the safety of these products . 
 however , additional steps such as chemical and biological standardization 
 would help improve the reproducibility of botanical dietary supplement 
 preparations , while additional adme studies and clinical investigations 
 of drug  botanical interactions would enhance our understanding 
 of the safe use of these products . gradually , basic science investigations 
 of mechanisms of action and identification of active compounds will 
 facilitate botanical dietary supplement standardization . then , definitive 
 clinical studies of efficacy and safety may be carried out that will 
 establish the safe use , health benefits , and limitations of these 
 products .
regulated 
 differently than drugs or foods , the market for botanical dietary 
 supplements continues to grow worldwide . the recently implemented 
 u.s . 
 fda regulation that all botanical dietary supplements must be 
 produced using good manufacturing practice is an important step toward 
 enhancing the safety of these products , but additional safeguards 
 could be implemented , and unlike drugs , there are currently no efficacy 
 requirements . to ensure a safe and effective product , botanical dietary 
 supplements should be developed in a manner analogous to pharmaceuticals 
 that involves identification of mechanisms of action and active constituents , 
 chemical standardization based on the active compounds , biological 
 standardization based on pharmacological activity , preclinical evaluation 
 of toxicity and potential for drug  botanical interactions , 
 metabolism of active compounds , and finally , clinical studies of safety 
 and efficacy . 
 completing these steps will enable the translation of 
 botanicals from the field to safe human use as dietary supplements .