SCIENTIFIC OPINION Scientific Opinion on the substantiation of a health claim related to ethanol-water extract of Caralluma fimbriata (Slimaluma ) and helps to reduce waist circumference pursuant to Article 13(5) of Regulation (EC) No 1924/2006 1 EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) 2, 3 European Food Safety Authority (EFSA), Parma, Italy This scientific output, published on 18 May 2010, replaces the earlier version published on 12 May 2010 4. ABSTRACT Following an application from Gencor Pacific Inc. submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of United Kingdom, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related to ethanolwater extract of Caralluma fimbriata (Slimaluma ) and helps to reduce waist circumference. Slimaluma is an ethanol-water extract of Caralluma fimbriata standardised by its content in pregnane glycosides that is sufficiently characterised. The Panel considers that a reduction in waist circumference, if accompanied by improvement in adverse health effects of an excess abdominal fat, is a beneficial physiological effect. One human intervention provided reported a statistically significant effect of ethanol-water extract of Caralluma fimbriata on the reduction of waist circumference in humans compared to a suitable control. No significant differences in body weight, body fat, blood glucose or lipid profiles were observed over time between the two groups. In weighing the evidence, the Panel took into account that whilst waist circumference was significantly reduced in the experimental group compared to placebo after 60 days of intervention in one of the human studies presented assessing this outcome, no significant effect of the ethanol-water extract of Caralluma fimbriata on waist circumference leading to an improvement in adverse health effects associated with an excess abdominal fat was observed when compared to a suitable control. The Panel concludes that a cause and effect relationship has not 1 On request from Gencor Pacific Inc., Question No EFSA-Q-2010-00027, adopted on 30 April 2010. 2 Panel members: Carlo Agostoni, Jean-Louis Bresson, Susan Fairweather-Tait, Albert Flynn, Ines Golly, Hannu Korhonen, Pagona Lagiou, Martinus Løvik, Rosangela Marchelli, Ambroise Martin, Bevan Moseley, Monika Neuhäuser-Berthold, Hildegard Przyrembel, Seppo Salminen, Yolanda Sanz, Sean (J.J.) Strain, Stephan Strobel, Inge Tetens, Daniel Tomé, Hendrik van Loveren and Hans Verhagen. Correspondence: nda@efsa.europa.eu 3 Acknowledgement: The Panel wishes to thank Joanne A. Harrold and the members of the Working Group on Claims for the preparatory work on this opinion: Carlo Agostoni, Jean-Louis Bresson, Susan Fairweather-Tait, Albert Flynn, Ines Golly, Marina Heinonen, Hannu Korhonen, Martinus Løvik, Ambroise Martin, Hildegard Przyrembel, Seppo Salminen, Yolanda Sanz, Sean (J.J.) Strain, Inge Tetens, Hendrik van Loveren and Hans Verhagen. 4 After publication of this opinion, the applicant notified to EFSA that changes in waist circumference between the intervention and placebo groups in the study by Kuriyan et al. (2007) had been erroneously reported in the opinion as statistically non significant, while these changes are significant. The opinion has been changed accordingly. This change does not affect the conclusions of the opinion as reducing waist circumference is not a beneficial physiological effect per se, but only if accompanied by an improvement in adverse health effects associated with an excess abdominal fat. In this context section 2 has been modified to indicate more clearly this fact. Where changes have been made to the opinion footnotes have been included to indicate the original text. Suggested citation: EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to ethanol-water extract of Caralluma fimbriata (Slimaluma ) and helps to reduce waist circumference pursuant to Article 13(5) of Regulation (EC) No 1924/2006.. [11 pp.]. doi:10.2903/j.efsa.2010.1602. Available online: www.efsa.europa.eu European Food Safety Authority, 2010 1
been established between the consumption of the ethanol-water extract of Caralluma fimbriata Slimaluma and a reduction in waist circumference leading to an improvement in adverse health effects associated with an excess abdominal fat. KEY WORDS Slimaluma, Caralluma fimbriata, pregnane glycosides, waist circumference, health claims. SUMMARY Following an application from Gencor Pacific Inc. submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of United Kingdom, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related to ethanol-water extract of Caralluma fimbriata (Slimaluma ) and helps to reduce waist circumference. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food constituent that is the subject of the health claim is an ethanol-water extract of Caralluma fimbriata (Slimaluma. The ethanol-water extract of the aerial parts of Caralluma fimbriata is the source of the ingredients in Slimaluma claimed as active by the applicant. The specific extraction and subsequent manufacturing processes are specified for the content of pregnane glycosides (at least 25 % by weight), which are claimed by the applicant to be the active ingredients for appetite control, of saponin glycosides (at least 10 % by weight) and of bitters (at least 3 % by weight). The Panel considers that the food constituent, ethanol-water extract of Caralluma fimbriata (Slimaluma ), which is the subject of the health claim, is sufficiently characterised. The claimed effect is helps to reduce waist circumference. The target population is overweight adults (i.e., 18 years of age). The Panel considers that the reduction in waist circumference, if accompanied by improvement in adverse health effects of an excess abdominal fat, is a beneficial physiological effect 5. Thirteen publications were identified by the applicant as being pertinent to the claim. The references provided included in vitro studies, intervention studies and reviews on the relationship between waist circumference and cardiovascular events, the reliability and validity of Visual Analogue Scales for the assessment of appetite, the central control of body weight and appetite, the link between leptin and obesity, the impact of soluble fibres or multivitamin and mineral supplements on body weight and mitotic clonal expansion. The Panel considers that no conclusions can be drawn from these references for the substantiation of the claimed effect. Among the publications submitted, two published human intervention studies reporting on measures of waist circumference, an unpublished animal study and an unpublished in vitro study investigated the effects of ethanol-water extract of Caralluma fimbriata. The first human study was a double blind, placebo controlled, randomised intervention in 62 healthy overweight and obese volunteers. The experimental group received 1 g of ethanol-water extract of Caralluma fimbriata per day for 60 days whilst the placebo group received maltodextrin capsules. At baseline and at the end of 30 and 60 days of intervention anthropometric measurements, including waist circumference, were obtained. Body weight, body fat, fasting blood glucose and lipid profiles (triglyceride, total and HDL cholesterol) were also measured at the same time points. A statistically 5 Original text: The Panel considers that the reduction in waist circumference might be a beneficial physiological effect. 2
significant reduction in waist circumference was observed in the intervention group compared to placebo at the end of study. No significant differences in body weight, body fat, blood glucose or lipid profiles were observed over time between the two groups. The Panel notes that the reduction in waist circumference observed in the intervention group compared to placebo was not associated to a reduction in body fat and did not lead to an improvement in adverse health effects associated with an excess abdominal fat (e.g., a reduction in blood glucose and/or an improvement in the lipid profile) 6. The second human study was a placebo-controlled, randomised intervention in 26 overweight volunteers. The experimental group received one 500 mg capsule of ethanol-water extract of Caralluma fimbriata 30 minutes before each meal for four weeks. The nature of the placebo was not specified. Thirteen subjects in the experimental group reduced their waist circumference compared to baseline. The impact of the intervention on the waist circumference of participants in the placebo group was not reported. It is also not reported whether the reductions in waist circumference observed in the experimental group reached statistical significance when compared to the placebo group. The Panel did not receive any further clarification from the applicant on this point. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claimed effect. The Panel considers that the results from the animal study and the one in vitro study do not predict an effect of the ethanol-water extract of Caralluma fimbriata Slimaluma on a reduction of waist circumference in humans. In weighing the evidence, the Panel took into account that whilst waist circumference was significantly reduced in the experimental group compared to placebo after 60 days of intervention in one of the human studies presented assessing this outcome, no significant effect of the ethanol-water extract of Caralluma fimbriata on waist circumference leading to an improvement in adverse health effects associated with an excess abdominal fat was observed when compared to a suitable control 7. The Panel concludes that a cause and effect relationship has not been established between the consumption of the ethanol-water extract of Caralluma fimbriata Slimaluma and a reduction in waist circumference leading to an improvement in adverse health effects associated with an excess abdominal fat 8. 6 Original text: No significant differences in waist circumference were observed between the two groups over the duration of the study. No significant differences in blood glucose or lipid profiles were observed over time between the two groups. 7 Original text: In weighing the evidence, the Panel took into account that in the one human study assessing changes in waist circumference no significant effect of the ethanol-water extract of Caralluma fimbriata on waist circumference was observed when compared to a suitable control. 8 Original text: The Panel concludes that a cause and effect relationship has not been established between the consumption of the ethanol-water extract of Caralluma fimbriata Slimaluma and a reduction in waist circumference. 3
TABLE OF CONTENTS Abstract... 1 Summary... 2 Table of contents... 4 Background as provided by the European Commission... 5 Terms of reference as provided by the European Commission... 5 Information provided by the applicant... 7 Assessment... 7 1. Characterisation of the food/constituent... 7 2. Relevance of the claimed effect to human health... 8 3. Scientific substantiation of the claimed effect... 8 Conclusions... 10 Documentation provided to EFSA... 10 References... 10 Glossary / Abbreviations... 11 4
BACKGROUND AS PROVIDED BY THE EUROPEAN COMMISSION Regulation (EC) No 1924/2006 9 harmonises the provisions that relate to nutrition and health claims and establishes rules governing the Community authorisation of health claims made on foods. As a rule, health claims are prohibited unless they comply with the general and specific requirements of that Regulation and are authorised in accordance with this Regulation and included in the lists of authorised claims provided for in Articles 13 and 14 thereof. In particular, Article 13(5) of that Regulation lays down provisions for addition of claims (other than those referring to the reduction of disease risk and to children s development and health), which are based on newly developed scientific evidence or include a request for the protection of proprietary data, to the Community list of permitted claims referred to in Article 13(3). According to Article 18 of that Regulation, an application for inclusion in the Community list of permitted claims referred to in Art 13(3) shall be submitted by the applicant to the national competent authority of a Member State, who will make the application and any supplementary information supplied by the applicant available to the European Food Safety Authority (EFSA). STEPS TAKEN BY EFSA: The application was received on 12/01/2010. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The scientific evaluation procedure started on 20/01/2010. On 26/03/2010, the NDA Panel agreed on the List of Questions which requests the applicant to supplement additional particulars to accompany the application. The applicant submitted the responses to the NDA Panel List of Questions on 13/04/2010. During the meeting on 30/04/2010, the NDA Panel, after having evaluated the overall data submitted, adopted an opinion on the scientific substantiation of a health claim related to ethanol-water extract of Caralluma fimbriata (Slimaluma ) and helps to reduce waist circumference. TERMS OF REFERENCE AS PROVIDED BY THE EUROPEAN COMMISSION EFSA is requested to evaluate the scientific data submitted by the applicant in accordance with Article 16(3) of Regulation (EC) No 1924/2006. On the basis of that evaluation, EFSA will issue an opinion on the scientific substantiation of a health claim related to: ethanol-water extract of Caralluma fimbriata (Slimaluma ) and helps to reduce waist circumference. EFSA Disclaimer The present opinion does not constitute, and cannot be construed as, an authorisation to the marketing of ethanol-water extract of Caralluma fimbriata (Slimaluma ), a positive assessment of its safety, nor a decision on whether ethanol-water extract of Caralluma fimbriata (Slimaluma ) is, or is not, classified as a foodstuff. It should be noted that such an assessment is not foreseen in the framework of Regulation (EC) No 1924/2006. 9 European Parliament and Council (2006). Regulation (EC) No 1924/2006 of the European Parliament and of the Council of 20 December 2006 on nutrition and health claims made on foods. Official Journal of the European Union OJ L 404, 30.12.2006. Corrigendum OJ L 12, 18.1.2007, p. 3 18. 5
It should also be highlighted that the scope, the proposed wording of the claim and the conditions of use as proposed by the applicant may be subject to changes, pending the outcome of the authorisation procedure foreseen in Article 18(4) of Regulation (EC) No 1924/2006. 6
INFORMATION PROVIDED BY THE APPLICANT Applicant s name and address: Gencor Pacific Inc, 301 Kam On Building, 176A Queen s Road, Central, (Hong Kong). Food/constituent as stated by the applicant Ethanol-water extract of Caralluma fimbriata (Slimaluma ). Health relationship as claimed by the applicant Slimaluma is specified for the content of pregnane glycosides. According to in vitro and in vivo studies, these active ingredients act on two levels by blocking the growth of pre-adipocytes and reducing the level of leptin. These immature cells are the source of adipocytes which absorb fat and produce leptin, a hormone involved in the long-term regulation of bodyweight. High levels of leptin are found in overweight and obese people. In human trials, these observed in vivo effects translate into a significant reduction in the feelings of hunger and a reduction in the waist circumference of overweight people who consume Slimaluma as part of a healthier lifestyle. Wording of the health claim as proposed by the applicant Slimaluma helps reduce waist circumference. Specific conditions of use as proposed by the applicant The target population are people who are overweight and aged 18 years old and over. According to the applicant, the quantity of the food/constituent and pattern of consumption required to obtain the claim comprises 500 mg of Slimaluma to be taken 1 hour prior to consuming a main meal (lunch and dinner). ASSESSMENT 1. Characterisation of the food/constituent The food constituent which is the subject of the health claim is ethanol-water extract of Caralluma fimbriata (Slimaluma ). The ethanol-water extract of the aerial parts of Caralluma fimbriata is the source of the ingredients in Slimaluma claimed as active by the applicant. The specific extraction and subsequent manufacturing processes are described in detail and are specified for the content of pregnane glycosides (at least 25 % by weight), which are claimed by the applicant to be the active ingredients for appetite control, of saponin glycosides (at least 10 % by weight) and of bitters (at least 3 % by weight). Pregnane glycosides are plant steroids which are common to all the Caralluma genus and various congeners are found in all Caralluma species. The key pregnane glycosides in Caralluma fimbriata extract are caratuberside A, caratuberside B and various congeners of bouceroside. Pregnane glycosides can be separated, identified and quantified by established methods (HPLC). 7
The Panel considers that the food constituent, ethanol-water extract of Caralluma fimbriata (Slimaluma ), which is the subject of the health claim, is sufficiently characterised. 2. Relevance of the claimed effect to human health The claimed effect is helps to reduce waist circumference. The target population is overweight adults (i.e., 18 years of age). A reduction in waist circumference may result from a reduction in abdominal fat and/or a reduction in body water. If associated with a reduction in abdominal fat, a reduction in waist circumference may lead to an improvement in adverse health effects of an excess abdominal fat, and particularly visceral fat (e.g. improved blood glucose control, blood lipid profile). However, a reduction in waist circumference owing to a reduction in body water is not associated with such effects 10. The Panel considers that the reduction in waist circumference, if accompanied by improvement in adverse health effects of an excess abdominal fat, is a beneficial physiological effect 11. 3. Scientific substantiation of the claimed effect The applicant reported to have conducted a literature search in PubMed for articles published in the English language between 1970 and 2009 without restriction to population subgroup or study type using the following search terms: Caralluma, pregnane glycosides, steroid glycosides, appetite, satiety, food intake, food consumption, weight loss, weight control, diet, waist size, waist circumference and anthropometry. A total of 13 publications were included in the application for the scientific substantiation of the health claim. The references provided included in vitro studies, intervention studies and reviews on the relationship between waist circumference and cardiovascular events, the reliability and validity of Visual Analogue Scales for the assessment of appetite, the central control of body weight and appetite, the link between leptin and obesity, the impact of soluble fibres or multivitamin and mineral supplements on body weight and mitotic clonal expansion. The Panel considers that no conclusions can be drawn from these references for the substantiation of the claimed effect. Among the publications submitted, two published human intervention studies (Kuriyan et al., 2007; Lawrence and Choudhary, 2004), an unpublished animal study (Kamalakkannan, unpublished, a) and an unpublished in vitro study (Kamalakkannan, unpublished, b) investigated the effects of ethanolwater extract of Caralluma fimbriata on different outcomes. The two human intervention studies reported on measures of waist circumference. Kuriyan et al. (2007) conducted a double blind, placebo controlled, randomised intervention in 62 (23 male and 39 female) healthy overweight and obese (BMI > 25 kg/m 2 ) Indian volunteers aged between 25 and 60 years. The 50 subjects who completed the trial were evenly distributed between experimental and placebo groups. The experimental group received 1 g of ethanol-water extract of Caralluma fimbriata per day for 60 days (in the form of two 500 mg capsules) whilst the placebo group received maltodextrin capsules (two 500 mg capsules). All subjects were also provided with the same standard advice regarding diet and physical activity targeted to achieve a weight loss of 5-10 % body weight over the study period. At baseline and at the end of 30 and 60 days of intervention anthropometric measurements, including waist circumference, were obtained. Body weight, body fat, 10 Original text: The reduction in waist circumference may lead to an improvement in the adverse health effects of an excess abdominal fat, and particularly visceral fat. However, a reduction in waist circumference owing to a reduction in body water is not considered per se as a beneficial physiological effect. 11 Original text: The Panel considers that the reduction in waist circumference might be a beneficial physiological effect. 8
fasting blood glucose and lipid profiles (triglyceride, total and HDL cholesterol) were also measured at the same time points. A statistically significant reduction in waist circumference was observed in the intervention group compared to placebo at the end of study. No significant differences in body weight, body fat, blood glucose or lipid profiles were observed over time between the two groups. The Panel notes that the reduction in waist circumference observed in the intervention group compared to placebo was not associated with a reduction in body fat and did not lead to an improvement in adverse health effects associated with an excess abdominal fat (e.g., a reduction in blood glucose and/or an improvement in the blood lipid profile) 12. Lawrence and Choudhary (2004) conducted a placebo controlled, randomised intervention in 26 (9 males) overweight volunteers aged between 31 and 73 years. Nineteen subjects were assigned to the active group and seven to the placebo group. Twenty four subjects completed the trial; each group had one drop out. The experimental group received one 500 mg capsule of ethanol-water extract of Caralluma fimbriata 30 minutes before each meal for four weeks. The nature of the placebo was not specified. All subjects were instructed not to change their daily activity or pattern of food intake over the period of the study. They were also informed not to change their diet in any way from four weeks preceding the study. Waist circumference was measured at baseline and at the end of four weeks of intervention. The impact of the intervention on the waist circumference of participants in the placebo group was not reported. It is also not reported whether the reduction in waist circumference observed in the experimental group reached statistical significance when compared to the placebo group. The Panel did not receive any further clarification from the applicant on this point. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claimed effect. One intervention study on rats (Kamalakkannan et al., unpublished, a) investigating the effects of different doses (5, 10, and 20 mg/d) of an ethanol-water extract of Caralluma fimbriata containing 25 % pregnane glycosides in the context of a cafeteria diet for 90 days on feed intake, body weight, serum leptin and atheromatous plaque formation, and one in vitro study (Kamalakkannan et al., unpublished, b) investigating the effects of Slimaluma on pre-adipocyte cell division were also presented. The Panel considers that the results from these studies do not predict an effect of the ethanol-water extract of Caralluma fimbriata Slimaluma on a reduction of waist circumference in humans. In weighing the evidence, the Panel took into account that whilst waist circumference was significantly reduced in the experimental group compared to placebo after 60 days of intervention in one of the human studies presented assessing this outcome, no significant effect of the ethanol-water extract of Caralluma fimbriata on waist circumference leading to an improvement in adverse health effects associated with an excess abdominal fat was observed when compared to a suitable control 13. The Panel concludes that a cause and effect relationship has not been established between the consumption of the ethanol-water extract of Caralluma fimbriata Slimaluma and a reduction in waist circumference leading to an improvement in adverse health effects associated with an excess abdominal fat 14. 12 Original text: No significant differences in waist circumference were observed between the two groups over the duration of the study. No significant differences in blood glucose or lipid profiles were observed over time between the two groups. 13 Original text: In weighing the evidence, the Panel took into account that in the one human study assessing changes in waist circumference no significant effect of the ethanol-water extract of Caralluma fimbriata on waist circumference was observed when compared to a suitable control. 14 Original text: The Panel concludes that a cause and effect relationship has not been established between the consumption of the ethanol-water extract of Caralluma fimbriata Slimaluma and a reduction in waist circumference. 9
CONCLUSIONS On the basis of the data presented, the Panel concludes that: The food constituent, ethanol-water extract of Caralluma fimbriata (Slimaluma, which is the subject of the health claim, is sufficiently characterised. The claimed effect is helps to reduce waist circumference. The target population is overweight adults (i.e., 18 years of age). The reduction in waist circumference, if accompanied by improvement in adverse health effects of an excess abdominal fat, is a beneficial physiological effect 15. A cause and effect relationship has not been established between the consumption of ethanolwater extract of the Caralluma fimbriata Slimaluma and a reduction in waist circumference leading to an improvement in adverse health effects associated with an excess abdominal fat 16. DOCUMENTATION PROVIDED TO EFSA Health claim application on ethanol-water extract of Caralluma fimbriata (Slimaluma ) and helps to reduce waist circumference pursuant to Article or 13(5) of Regulation (EC) No 1924/2006 (Claim Serial No: 0266_UK). January 2010. Submitted by Gencor Pacific Inc. REFERENCES Kamalakkannan S, Rajendran R, Venkatesh RV and Akbarsha MA, unpublished, a. Anti-Obesegenic and Anti-Atherosclerotic Property of Caralluma fimbriata Extract. Kamalakkannan S, Rajendran R, Venkatesh RV and Akbarsha MA, unpublished, b. Effect of Caralluma fimbriata extract on 3T3-L1 pre-adipocyte cell division. Kuriyan R, Raj T, Srinivas SK, Vaz M, Rajendran R and Kurpad AV, 2007. Effect of Caralluma fimbriata extract on appetite, food intake and anthropometry in adult Indian men and women. Appetite, 48, 338-344. Lawrence RM and Choudhary S, 2004. Caralluma Fimbriata in the treatment of obesity. 12th Annual World Congress of Anti-Aging Medicine, December, Las Vegas, USA. 15 Original text: The claimed effect is helps to reduce waist circumference. The target population is overweight adults (i.e., 18 years of age). The reduction in waist circumference might be a beneficial physiological effect. 16 Original text: A cause and effect relationship has not been established between the consumption of ethanol-water extract of the Caralluma fimbriata Slimaluma and a reduction in waist circumference. 10
GLOSSARY / ABBREVIATIONS BMI Body mass index HPLC LDL High performance liquid chromatography Low-density lipoproteins 11