SCIENTIFIC OPINION Scientific Opinion on the substantiation of a health claim related to ethanol-water extract of Caralluma fimbriata (Slimaluma ) and helps to control hunger/appetite 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 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 control hunger/appetite. Slimaluma is an ethanol-water extract of Caralluma fimbriata standardised by its content in pregnane glycosides that is sufficiently characterised. A reduction of appetite leading to a reduction in subsequent energy intake might be beneficial physiological effect. A double blind, placebo controlled, randomised trial in humans investigating the effects of Slimaluma on appetite ratings and subsequent energy intake was considered as being pertinent to the claim. The mean hunger level of the experimental group was found to be significantly lower than that of the placebo group. No statistically significant differences in energy intake between the experimental and placebo groups were reported. 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 of appetite leading to a reduction in subsequent energy intake. KEY WORDS Slimaluma, Caralluma fimbriata, pregnane glycosides, hunger, appetite, energy intake, health claims. 1 On request from Gencor Pacific Inc., Question No EFSA-Q-2010-00031, 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. 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 control hunger/appetite pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA Journal; 8(5):1606. [10 pp.]. doi:10.2903/j.efsa.2010.1606. Available online: www.efsa.europa.eu European Food Safety Authority, 2010 1
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 control hunger/appetite. 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 control hunger/appetite. The target population is overweight adults (i.e., 18 years of age). The Panel considers that a reduction of appetite leading to a reduction in subsequent energy intake might be a beneficial physiological effect. Ten 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 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. Only one of the human intervention studies reported on measures of appetite and as such was considered pertinent to the claim. It 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 assessment of appetite was performed in the fasted state using four visual analogue scales for hunger, thoughts of food, urge to eat and fullness of stomach. At baseline and following 60 days of intervention, dietary intake was also assessed using a modified food frequency questionnaire. At day 60 only, the mean hunger level of the experimental group was found to be significantly lower than that of the placebo group. There were no significant differences reported for the other assessments of appetite over time within groups from baseline, or between the two groups. No differences in energy intake between the experimental and placebo groups were reported at day 60. The Panel notes that measurement of energy intake was via self-reported methods (rather than being measured directly within the laboratory), the validity of which is questionable. 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 the reduction of appetite in humans. In weighing the evidence, the Panel took into account that whilst the ratings of hunger were significantly reduced in the experimental group compared to placebo at day 60 in the one human study presented which assessed this outcome, no significant effect of the ethanol-water extract of Caralluma fimbriata on energy intake was observed when compared to a suitable control. 2
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 of appetite leading to a reduction in subsequent energy intake. 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... 9 Documentation provided to EFSA... 9 References... 9 Glossary / Abbreviations... 10 4
BACKGROUND AS PROVIDED BY THE EUROPEAN COMMISSION Regulation (EC) No 1924/2006 4 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 helps to control hunger/appetite. 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 helps to control hunger/appetite. 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. 4 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 in overweight people who consume Slimaluma as part of a healthier lifestyle. Wording of the health claim as proposed by the applicant Slimaluma helps to control hunger/appetite. 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). 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. 7
2. Relevance of the claimed effect to human health The claimed effect is helps to control hunger/appetite. The target population is overweight adults (i.e., 18 years of age). The claimed effect as proposed by the applicant is the reduction of appetite, which may contribute to the maintenance of energy balance and weight control by decreasing subsequent energy intake. The Panel considers that the methods (i.e. visual analogue scales, VAS) used for measuring the claimed effect under laboratory conditions in human studies are well established and reasonably robust. The Panel considers that a reduction of appetite leading to a reduction in subsequent energy intake might be beneficial physiological effect. 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 10 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 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. Only one of the human intervention studies reported on measures of appetite and as such was considered pertinent to the claim (Kuriyan et al., 2007). Kuriyan et al. (2007) conducted a double blind, placebo controlled, randomised trial 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 assessment of appetite was performed in the fasted state using four visual analogue scales for hunger, thoughts of food, urge to eat and fullness of stomach. The scales were administered in triplicate on each occasion with the average response recorded. At baseline and following 60 days of intervention, dietary intake was also assessed using a modified food frequency questionnaire developed specifically for the Indian study population. At day 60 only, the mean hunger level of the experimental group was found to be significantly lower than that of the placebo group. There were no significant differences reported for the other assessments of appetite over time between the two groups. No significant differences in energy intake between the experimental and placebo groups were reported at day 60. The Panel notes that measurement of energy intake was via self-reported methods (rather than being measured directly within the laboratory), the validity of which is questionable. 8
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 form these studies do not predict an effect of the ethanol-water extract of Caralluma fimbriata Slimaluma on the reduction of appetite in humans. In weighing the evidence, the Panel took into account that whilst the ratings of hunger were significantly reduced in the experimental group compared to placebo at day 60 in the one human study presented which assessed this outcome (Kuriyan et al., 2007), no significant effect of the ethanolwater extract of Caralluma fimbriata on energy intake was observed when compared to a suitable control. 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 of appetite leading to a reduction in subsequent energy intake. 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 control hunger/appetite. The target population is overweight adults (i.e., 18 years of age). A reduction of appetite leading to a reduction in subsequent energy intake might be a beneficial physiological effect. A cause and effect relationship has not been established between the consumption of the ethanol-water extract of Caralluma fimbriata Slimaluma and a reduction of appetite leading to a reduction in subsequent energy intake. DOCUMENTATION PROVIDED TO EFSA Health claim application on ethanol-water extract of Caralluma fimbriata (Slimaluma ) and helps to control hunger/appetite pursuant to Article or 13(5) of Regulation (EC) No 1924/2006 (Claim Serial No: 0270_UK). January 2010. Submitted by Gencor Pacific Inc. REFERENCES Kamalakkannan S, Rajendran R, Venkatesh RV, Akbarsha MA, unpublished, a. Anti-Obesegenic and Anti-Atherosclerotic Property of Caralluma fimbriata Extract. Kamalakkannan S, Rajendran R, Venkatesh RV, 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, 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, Choudhary S, 2004. Caralluma Fimbriata in the treatment of obesity. 12th Annual World Congress of Anti-Aging Medicine, December, Las Vegas, USA. 9
GLOSSARY / ABBREVIATIONS BMI Body mass index HPLC High performance liquid chromatography 10