Yoga in Women With Abdominal Obesity
A randomized controlled trial
; ; ; ;
Background: Abdominal obesity is a major risk factor for morbidity and mortality. The aim of this study was to investigate the effect of yoga on waist circumference and other anthropometric and self-reported variables in women with abdominal obesity.
Methods: 60 women with abdominal obesity (waist circumference ≥ 88 cm; body-mass index [BMI] ≥ 25) were randomly allocated in a 2:1 ratio to either a 12-week yoga intervention (n = 40) or a waiting list (n = 20). The waist circumference was the primary endpoint. Secondary (exploratory) endpoints included the waist/hip ratio, body weight, BMI, body fat percentage, body muscle mass percentage, blood pressure, health-related quality of life, self-esteem, subjective stress, body awareness, and body responsiveness, and the safety of the intervention. The persons assessing the outcomes were blinded to the group to which the patients belonged.
Results: The patients in the yoga group participated in a mean of 30.2±9.2 (maximum, 42) hours of supervised yoga practice. Their abdominal circumference was significantly reduced in comparison to the participants on the waiting list, with an intergroup difference of –3.8 cm (95% confidence interval [−6.1; –1,.5]; p = 0.001). There were further, moderate intergroup differences in the waist/hip ratio, body weight, BMI, body fat percentage, body muscle mass percentage, mental and physical well-being, self-esteem, subjective stress, body awareness, and trust in bodily sensations (all p<0.05). There were no serious adverse events. None of the participants embarked on a low-calorie diet while participating in the study.
Conclusion: The 12-week yoga intervention had moderately strong positive effects on anthropometric and self-reported variables in women with abdominal obesity. Yoga is safe in this population and can be recommended as a technique for combating abdominal obesity in women.
The prevalence of obesity worldwide is rising, especially in developing countries and newly industrializing countries. The point prevalence is higher in women (15%) than in men (11%), which corresponds to a relative risk of 1.4 (1). Especially abdominal obesity—an unfavorable accumulation of fat around the stomach, which is not limited to overweight persons—has been identified as an important risk factor for cardiovascular and metabolic disorders (2, 3). Since, in addition to inadequate eating habits, a sedentary lifestyle is the main cause of obesity (4), regular physical activity is recommended in the medical guidelines as the most important therapeutic option in non-morbid obesity (5). However, the fact that a substantial proportion of obese persons does not adhere to such recommendations (6) provides a legitimate reason for studying alternative forms of physical activity to reduce weight.
Yoga is one such alternative form of physical activity that is used increasingly for the purpose of health promotion (7, 8). In North America and Europe, yoga comprises mainly body postures (asanas), breathing exercises (pranayama), and meditation (dhyana). Yoga is also gaining increasing popularity as a therapeutic measure. Some 80% of persons practicing yoga in the US (more than 16 million people) reported that they had taken up the practice with the explicit goal of improving their health (10, 11). In this setting, the hope to lose weight was one of the most important reasons for taking up yoga (12).
Although initial evidence for the effectiveness of yoga on weight control and improved body composition from surveys (13) and clinical studies (14) is now available, the effects of yoga on abdominal obesity have not been investigated to date. Our study investigated the effect of yoga on waist circumference and further anthropometric measures in women with abdominal obesity.
The study was conceived as a single center, single blinded randomized controlled trial (RCT). Before patients were recruited, the study was approved by the ethics committee at the University of Duisburg-Essen (approval number 15–6194-BO), and it was registered with ClinicalTrials.gov (registration number NCT02420145). The study was conducted and reported in accordance with the CONSORT 2010 statement (15).
Participants were recruited by placing announcements in the local press and by using email lists from local businesses. Women who expressed an interest underwent a telephone interview with a study assistant and were invited for a medical examination after an initial selection had been made. The exam included a physical examinationi as well as medical and medication histories. Suitable participants (Box) received detailed information in written and verbal form, and written consent was obtained from these women.
The participants were allocated to a yoga group or a control group by using a randomized block design with randomly varying block lengths. The randomization list was set out by a biometrician who was not involved in patient recruitment or data collection and who used random allocation software (16). The list was password protected, and only the biometrician had access to it. After written consent had been received and the initial data collection had been completed, participants were centrally randomized by the biometrician.
Yoga: The yoga intervention consisted of an initial full-day workshop, followed by two weekly 90-minute classes of traditional hatha yoga over a 12-week period. The yoga classes were based on integral yoga as developed by Swami Sivananda and an adaptation of the basic yoga-vidya sequence (17). eBoxes 1 and 2 show further details of the yoga program.
Waiting list: The women who had been allocated to the control group were entered into a waiting list and did not participate in any study interventions during the initial 12 weeks of the study. They were asked not to practice yoga during that period and to not change their habitual physical activities. After the end of the 12th week, subjects were free to participate in a yoga program identical to that of the intervention group. The purpose was to motivate participants. No further data were collected.
The outcome assessment was conducted by persons who had been blinded to the group allocation and had not been involved in patient recruitment, randomization, or interventions. Participants were explicitly asked not to mention their group allocation to these persons, and both parties were instructed to restrict their communication to collecting anthropometric measurements and questionnaire data.
As our primary outcome measure we defined waist circumference at week 12. Secondary researcher-assessed measures defined a priori included the waist-hip ratio, body weight, body mass index (BMI), bioelectrical impedance analysis, and blood pressure (eBox 1). Secondary patient-reported measures defined a priori included:
- Quality of life, collected by administering the short form-36 health survey (SF-36) (18)
- Self esteem, collected by using Rosenberg’s self esteem scale (19)
- Perceived stress, determined by using the German 10-item version of the perceived stress scale (20), and
- Body awareness, collected by using the German 17-item version of the body awareness questionnaire (21)
- Body responsiveness, captured by using the German two-factorial 6-item version of the body responsiveness scale (22).
All adverse events that occurred during the study period were documented (eBox 1).
Sample size calculation and statistical evaluation
We calculated the required sample size a priori on the basis of a study from South Korea, which compared yoga versus “no intervention” in postmenopausal obese women (23). On the basis of this study, a group difference of d=1.02 in waist circumference was expected. If this effect is assumed, a t test with a two-sided significance level of α = 0.05 requires a total of 48 participants in order to determine a difference between groups with 90% power if a 2:1 allocation ratio is applied. In order to avoid a potential loss in power owing to a dropout rate of up to 20% of study participants, we planned to include 60 subjects into the study and to assign 40 participants to the yoga group and 20 participants to the control group.
We analyzed the outcome measures on the basis of the intention to treat principle. All randomized participants were included in the analysis, independently of whether a complete dataset was available or whether the study was conducted according to the protocol. Missing values were multiply imputed by using the Markov chain Monte Carlo procedure (24, 25). This yielded a total of 50 complete datasets. Additionally, we conducted sensitivity analyses for the main outcome measure, by including, on the one hand, only participants with complete datasets and, on the other hand, only the per protocol population—that is, participants with complete datasets who had participated in at least 18 yoga units and the initial workshop.
We used Students's t tests for continuous data and the chi-square test for categorical data to analyze possible differences in sociodemographic or anthropometric parameters at baseline.
Waist circumference at week 12 was defined as the primary outcome measure and was evaluated by using univariate analysis of covariance (ANCOVA), with the outcome measure modeled as a function of group allocation (two classes) and the respective baseline value (linear covariate), in order to achieve an overall effect estimate, the 95% confidence interval, and the P-value. All other variables were defined as secondary outcome measures and were analyzed exploratively by using analog ANCOVA models.
As a measure of the clinical relevance of the results, we compared the number of participants in both groups, which by week 12 had achieved a clinically relevant reduction in their waist circumference of at least 5% (26). Furthermore, we calculated the number needed to treat (NNT). In order to assess the safety of the intervention we used the chi-square test to compare the number of participants in both groups who experienced adverse events during the study period. All analyses were done by using SPSS software (Statistical Package for Social Sciences-Software, Statistics for Windows, Version 22.0, Armonk, NY, USA: IBM Group).
In total we surveyed 123 women in telephone interviews, 60 of whom were excluded because of a lack of interest or because they did not meet the inclusion criteria (Figure). A study physician examined 63 women in order to ascertain their eligiblity for inclusion in the study; 3 of those women were excluded. 60 women met all inclusion criteria and were included in the study after they had given informed consent; these were randomized into the yoga group (n=40) and the control group (n=20). Three participants in the yoga group (7.5%) and one participant in the control group (5%) did not complete the second data collection in week 12 (Figure).
Table 1 shows participants’ sociodemographic and anthropometric characteristics. The participants’ mean age was 47.8±8.2 years, most were married or in long-term relationships, had (vocational) A level equivalents, and were in work. Some participants had previous experiences with yoga.
No significant differences existed between the groups with regard to sociodemographic data. The mean waist circumference was 104.3±10.3 cm, the mean BMI was 34.2±5.4. At baseline, the participants in the control group had higher values in terms of height, hip circumference, BMI, and percentage of body fat compared with the participants in the yoga group (Table 1).
All participants in the yoga group participated in the initial full-day workshop; adherence to the intervention fell during the course of the study (figure 1). In total, the participants in the yoga group underwent a mean of 16.1±6.1 of a maximum of 24 yoga units (67.1%). This corresponds to an overall mean value of 30.2±9.2 of a maximum of 42 hours of supervised yoga practice (workshop plus weekly yoga sessions) (71.9%). Furthermore, they practiced a mean of 38.7±16.1 minutes at home (eFigure 2).
None of the participants started a calorie-reduced diet during the study period.
With regard to the primary outcome measure, participants in the yoga group were found to have a significantly lower waist circumference than those in the control group (P=0.001; Table 2).
The sensitivity analyses showed comparable results in the participants with complete datasets (difference between groups –3.7 cm; 95% confidence interval [–6.2; –1.2]; P=0.004) and in the per-protocol analysis (between group difference –4.8 cm; [–7.5;–2.0]; P=0.001).
13 participants in the yoga group (32.5%) achieved a clinically relevant reduction in waist circumference of at least 5%, compared with 2 participants in the control group (10.0%). This corresponds to an NNT of 4.3 [2.4; 33.3].
Further differences between the groups were observed for the waist-hip ratio (P=0.034), body weight (P=0.003), BMI (P=0.008), percentage of body fat (P=0.007), and percentage of body muscle mass (P=0.010; Table 1). No differences between groups were observed for systolic (P=0.446) and diastolic (P=0.709) blood pressure.
Regarding health related quality of life, differences between the groups were observed in week 12 in favor of the yoga group, on the physical (P=0.018) and mental component score (P=0.009) and all subscales of health related quality of life (P<0.05), with the exception of the subscale for emotional role functioning (Table 3). Further differences between the groups were found with regarding to self esteem (P<0.002), perceived stress (P=0.016), body awareness (P=0.001), and the subscale “trust in bodily sensations” (subscale of the body responsiveness scale) (P<0.001); Table 3).
Safety: no serious adverse events occurred. 13 women (32.5%) in the yoga group experienced 16 mild adverse effects; 5 women in the control group (25.0%) experienced a total of 6 mild adverse effects (P=0.550; eBox 1).
In the present randomized trial of women with abdominal obesity, participation in an intensive 12-week yoga intervention led to a positive—if not very pronounced—change in anthropometric measures, quality of life, and mental health, while incurring only a small number of adverse events.
Thus far, only few randomized studies have explicitly focused on the effect of yoga on anthropometric measures in overweight or obese persons. On the basis of the few available studies, recent meta-analyses showed that yoga was effective with regard to anthropometric variables in overweight or obese persons as well as in patients with type 2 diabetes or other cardiovascular risk constellations (14, 27).
However, as far as we are aware, no study to date has investigated the effect of yoga on waist circumference in otherwise healthy women with abdominal obesity. Since abdominal obesity is a much stronger predictor for the risk of cardiovascular disorders than body weight or the BMI (2, 3), our study closes an important gap in assessing the effectiveness of yoga regarding cardiovascular risk.
The existing publications give rise to the assumption that the effects of yoga on anthropometric measures can be increased by a greater frequency, a longer duration, and the use of complex yoga interventions with multiple components and in combination with dietary/nutritional recommendations (especially of a vegetarian diet with or without calorie reduction) and homework (28). Accordingly, these factors were considered in developing the intervention in the present study.
While yoga lessons for beginners are associated with little intense physical activity and therefore do not meet the recommendations for adequate cardiovascular exercise (29), more intensive styles of yoga can lead to higher energy consumption (29, 30) and thus contribute to weight loss and weight control (13). However, we think that it is unlikely that the identified anthropometric effects of the intervention are due exclusively to the increase in physical activity: the reduction in the proportion in body fat that was achieved in the yoga group corresponds to a reduction of 1.3 kg of pure fat, or 12 000 kcal. The mean energy expenditure in yoga (including yoga postures, breathing exercises, and meditation) is 2.2–3.2 kcal/minute (29, 31); higher values can be assumed for overweight participants (32). Accordingly, a conservative estimate would mean that the effect we found would require a yoga exercise commitment of between 63 and 92 hours, whereas the mean practice time in our study amounted to just under 38 hours. However, an interpretation that is based on physical activity only and does not consider other possible mechanisms of action is not far reaching enough: the practice of yoga can reduce back pain and joint pain (33, 34) and increase the extent of other physical activity (not associated with yoga) (35).
In addition to physical activity, the yoga intervention in the present study also comprised yoga-based nutritional advice and psychologically oriented elements, such as relaxation techniques, meditation, breathing exercises, and instructions for positive thinking. Yoga has been shown to alleviate chronic depression, stress, and other psychological disorders (36–38). This could mean a reduction in overeating to compensate for negative feelings (emotional eating) and the resultant overweight (39). Accordingly, the mechanisms of action of the yoga intervention presented in this article might include a reduction in the physical factors (inadequate physical activity and diet) as well as the emotionally sustaining factors (emotional eating) underlying obesity. The comparatively good effectiveness of the intervention investigated in the present study may be due to this combination of different components.
Our study has several limitations. The control group did not provide a control for attention-related unspecific effects or regression to the mean: while the participants in the intervention group may have experienced positive effects owing to expectation-related effects, participants in the control group may have experienced negative effects as a result of being disappointed about their group allocation. Furthermore, it was not possible to exclude completely independent participation in a yoga class outside the study setting by fundamentally motivated participants who had been allocated to a waiting-control group, which may bias the results. It was not possible to blind participants with regard to their allocated intervention. The study used an intensive program of yoga, and its results can therefore not be generalized to other, less intensive, yoga programs. Adherence to the intervention decreased over the course of the study. In spite of randomization, differences between the groups—by definition random—in terms of anthropometric variables occurred at the start of the study, although their effect was minimized by our use of analyses of covariance (40).
Implications for clinical practice
Future studies should investigate the effectiveness of yoga compared with other types of sports and nutritional programs and should study the long-term effects of the intervention. Studies should also investigate the generalizability to other populations, especially men. The dose-response relation should be investigated, especially with regard to adherence, which was very low towards the end of the study.
An intensive yoga intervention lasting 12 weeks including women with abdominal obesity reduced participants’ waist circumference, waist-hip ratio, body weight, BMI, and percentage of body fat and increased the percentage of muscle mass. Yoga improved participants’ mental and physical wellbeing and self esteem, and reduced their perceived stress. As the intervention constitutes a safe and effective intervention in this population, yoga can be recommended to women in order to reduced their abdominal obesity.
We thank the professional association of Yoga Vidya Teachers (BYV), especially Vera Bohle and Vicara Shakti Müller, for their help in developing the yoga intervention, and Sonja Omlor for her support with patient recruitment and data collection.
Yoga Vidya reg. assoc. has reimbursed Ms Thoms for travel expenses. The remaining authors declare that no conflict of interest exists.
Manuscript received on 14 March 2016, revised version accepted on
16 June 2016.
Translated from the original German by Birte Twisselmann, PhD.
PD Dr. rer. medic. Holger Cramer
Klinik für Naturheilkunde und Integrative Medizin,
Am Deimelsberg 34a
45276 Essen, Germany
For eReferences please refer to:
University of Duisburg-Essen, Essen, Germany: PD Dr. rer. medic. Cramer, Ms Thoms, Mr Anheyer,
Dr. rer. medic. Lauche, Prof. Dr. med. Dobos
Australian Research Centre in Complementary and Integrative Medicine (ARCCIM), University of Technology Sydney, Australia: PD Dr. rer. medic. Cramer, Dr. rer. medic. Lauche
|1.||World Health Organization: Global status report on noncommunicable diseases 2014. Geneva: WHO Press; 2014.|
|2.||Westphal SA: Obesity, abdominal obesity, and insulin resistance. Clin Cornerstone 2008; 9: 23–9 CrossRef|
|3.||Yusuf S, Hawken S, Ounpuu S, et al.: Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364: 937–52 CrossRef|
|4.||Cecchini M, Sassi F, Lauer JA, Lee YY, Guajardo-Barron V, Chisholm D: Tackling of unhealthy diets, physical inactivity, and obesity: health effects and cost-effectiveness. Lancet 2010; 376: 1775–84 CrossRef|
|5.||American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Obesity Expert Panel: Guidelines (2013) for the management of overweight and obesity in adults. Obesity (Silver Spring) 2014; 22 Suppl 2: S5–39.|
|6.||Castellani W, Ianni L, Ricca V, Mannucci E, Rotella CM: Adherence to structured physical exercise in overweight and obese subjects: a review of psychological models. Eat Weight Disord 2003; 8: 1–11 CrossRef|
|7.||Feuerstein G: The yoga tradition. Prescott: Hohm Press 1998.|
|8.||Iyengar BKS: Light on Yoga. New York: Schocken Books 1966.|
|9.||De Michelis E: A History of Modern Yoga: Patanjali and Western Esotericism. London, UK: Continuum International Publishing Group 2005.|
|10.||Birdee GS, Legedza AT, Saper RB, Bertisch SM, Eisenberg DM, Phillips RS: Characteristics of yoga users: results of a national survey. J Gen Intern Med 2008; 23: 1653–8 CrossRef MEDLINE PubMed Central|
|11.||Cramer H, Ward L, Steel A, Lauche R, Dobos G, Zhang Y: Prevalence, Patterns, and Predictors of Yoga Use: Results of a U.S. Nationally Representative Survey. Am J Prev Med 2016; 50: 230–5 CrossRef MEDLINE|
|12.||Park CL, Riley KE, Bedesin E, Stewart VM: Why practice yoga? Practitioners’ motivations for adopting and maintaining yoga practice. J Health Psychol 2014.|
|13.||Kristal AR, Littman AJ, Benitez D, White E: Yoga practice is associated with attenuated weight gain in healthy, middle-aged men and women. Altern Ther Health Med 2005; 11: 28–33 MEDLINE|
|14.||Lauche R, Langhorst J, Lee MS, Dobos G, Cramer H: A systematic review and meta-analysis on the effects of yoga on weight-related outcomes. Prev Med 2016; 87: 213–32 CrossRef MEDLINE|
|15.||Schulz KF, Altman DG, Moher D: CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann Intern Med 2010; 152: 726–32 CrossRef MEDLINE|
|16.||Saghaei M: Random allocation software for parallel group randomized trials. BMC Med Res Methodol 2004; 4: 26 CrossRef MEDLINE PubMed Central|
|17.||Vishnu-devananda S: The Complete Illustrated Book of Yoga. New York: Harmony 1995.|
|18.||Ware JE Jr., Sherbourne CD: The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30: 473–83 CrossRef MEDLINE|
|19.||Rosenberg M: Society and the adolescent self-image. Princeton: Princeton University Press 1965 CrossRef|
|20.||Cohen S, Kamarck T, Mermelstein R: A global measure of perceived stress. J Health Soc Behav 1983; 24: 385–96 CrossRef|
|21.||Shields SA: The body awareness questionnaire. Journal of personality Assessment 1989; 53: 802–15 CrossRef|
|22.||Daubenmier J: The relationship of yoga, body awareness, and body responsiveness to self-objectification and disordered eating. Psychology of Women Quaterly 2005; 29: 207–19 CrossRef|
|23.||Lee JA, Kim JW, Kim DY: Effects of yoga exercise on serum adiponectin and metabolic syndrome factors in obese postmenopausal women. Menopause 2012; 19: 296–301 CrossRef MEDLINE|
|24.||Rubin DB: Multiple Imputation for Nonresponse in Surveys. New York; John Wiley & Sons 1987 CrossRef|
|25.||Schafer JL: Analysis of Incomplete Multivariate Data. New York: Chapman and Hall 1997 CrossRef|
|26.||Verweij LM, Terwee CB, Proper KI, Hulshof CT, van Mechelen W: Measurement error of waist circumference: gaps in knowledge. Public Health Nutr 2013; 16: 281–8 CrossRef MEDLINE|
|27.||Cramer H, Lauche R, Haller H, Steckhan N, Michalsen A, Dobos G: Effects of yoga on cardiovascular disease risk factors: a systematic review and meta-analysis. Int J Cardiol 2014; 173: 170–83 CrossRef MEDLINE|
|28.||Rioux JG, Ritenbaugh C: Narrative review of yoga intervention clinical trials including weight-related outcomes. Altern Ther Health Med 2013; 19: 32–46 MEDLINE|
|29.||Hagins M, Moore W, Rundle A: Does practicing hatha yoga satisfy recommendations for intensity of physical activity which improves and maintains health and cardiovascular fitness? BMC Complement Altern Med 2007; 7: 40 CrossRef MEDLINE PubMed Central|
|30.||Mody BS: Acute effects of Surya Namaskar on the cardiovascular & metabolic system. J Bodyw Mov Ther 2011; 15: 343–7 CrossRefMEDLINE|
|31.||Clay CC, Lloyd LK, Walker JL, Sharp KR, Pankey RB: The metabolic cost of hatha yoga. J Strength Cond Res 2005; 19: 604–10 CrossRef MEDLINE|
|32.||Mcardle WD, Katch FI, Katch VL: Essentials of exercise physiology. Philadelphia: Lippincott Williams and Wilkins 2000.|
|33.||Cramer H, Lauche R, Haller H, Dobos G: A systematic review and meta-analysis of yoga for low back pain. Clin J Pain 2013; 29: 450–60 CrossRef MEDLINE|
|34.||Cramer H, Lauche R, Langhorst J, Dobos G: Yoga for rheumatic diseases: a systematic review. Rheumatology (Oxford) 2013; 52: 2025–30 CrossRef MEDLINE|
|35.||Bryan S, Pinto Zipp G, Parasher R: The effects of yoga on psychosocial variables and exercise adherence: a randomized, controlled pilot study. Altern Ther Health Med 2012; 18: 50–9 MEDLINE|
|36.||Cramer H, Lauche R, Langhorst J, Dobos G: Yoga for depression: a systematic review and meta-analysis. Depress Anxiety 2013; 30: 1068–83 CrossRef MEDLINE|
|37.||Chong CS, Tsunaka M, Tsang HW, Chan EP, Cheung WM: Effects of yoga on stress management in healthy adults: A systematic review. Altern Ther Health Med 2011; 17: 32–8 MEDLINE|
|38.||Klatte R, Pabst S, Beelmann A, Rosendahl JS: The efficacy of body-oriented yoga in mental disorders. Dtsch Arztebl Int 2016; 113: 195–202 MEDLINE|
|39.||Dallman MF, Pecoraro N, Akana SF, et al.: Chronic stress and obesity: a new view of „comfort food“. Proc Natl Acad Sci U S A 2003; 100: 11696–701 CrossRef MEDLINE PubMed Central|
|40.||Vickers AJ, Altman DG: Analysing controlled trials with baseline and follow up measurements. BMJ 2001; 323: 1123–4 CrossRef|
|e1.||World Health Organization: Waist circumference and waist–hip ratio: report of a WHO expert consultation. Geneva: World Health Organization (WHO) 2011.|
|e2.||Bosy-Westphal A, Later W, Hitze B, Sato T, Kossel E, Gluer CC, et al: Accuracy of bioelectrical impedance consumer devices for measurement of body composition in comparison to whole body magnetic resonance imaging and dual X-ray absorptiometry. Obes Facts 2008; 1: 319–24 CrossRef MEDLINE|
|e3.||Westhoff TH, Straub-Hohenbleicher H, Schmidt S, Tolle M, Zidek W, van der Giet M: Convenience of ambulatory blood pressure monitoring: comparison of different devices. Blood Press Monit 2005; 10: 239–42 CrossRef|
|e4.||Bundesministerium der Justiz und für Verbraucherschutz: Verordnung über die Anwendung der Guten Klinischen Praxis bei der Durchführung von klinischen Prüfungen mit Arzneimitteln zur Anwendung am Menschen (GCP-Verordnung – GCP-V). 2004. https://www.gesetze-im-internet.de/gcp-v/BJNR208100004.html (letzter Zugriff am 02. Mai 2016).|