Doi:10.1080/00365520903131999Scandinavian Journal of Gastroenterology, 2009; 44: 11861190 Effect of fat emulsion (Fabuless) on orocecal transit timein healthy men ARVO HAENNI1, BIRGITTA SUNDBERG2, NAHID YAZDANPANAH3,ANNIKA VIBERG4 & JOHAN OLSSON2 1Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Sweden, 2KPLGood Food Practice AB, Uppsala, Sweden, 3DSM Food Specialties, Delft, The Netherlands, and 4DSM, Food Specialties,Stockholm, Sweden AbstractBackground. Given the growing prevalence of overweight and related health consequences, there is increased interest inthe search for novel dietary strategies for weight control. A food ingredient, an emulsion based on palm and oat oil(Fabuless, previously known as Olibra), has been associated with short-term reductions of food intake, induction of satiety,alternation in the satiety hormones, as well as long-term effects on weight control. The mechanism by which it can exertthese effects is so far unclear, though it has been suggested that the ‘‘ileal break'' may play a role in increasing gastrointestinaltransit time. The aim of this study was to investigate the effects of this stable fat emulsion on orocecal transit time in healthymen. Material and methods. In a controlled, double-blind, cross-over-designed study, 15 healthy men (aged 2059 years,body mass index (BMI) 2228), randomly allocated to two treatments, consumed the stable fat emulsion or a milk fat inyoghurt during two days of investigation, with an interval of 1 week. Orocecal transit time was determined by followingblood sulfapyridine levels, which is a metabolite of salazopyrine in the colon. Results. A statistically significant delay inthe appearance of sulfapyridine in serum was obtained after active treatment versus control treatment, corresponding to a45-min longer orocecal transit time due to fat emulsion consumption. Conclusions. This study provides the first evidenceto suggest that this stable fat emulsion may affect the ileal brake mechanism by slowing down the gastrointestinal transittime, which might explain the weight control and appetite suppression previously observed in association with this emulsion.
Key Words: Appetite, ileal break, orocecal transit time, overweight, weight maintenance ‘‘Fabuless'' is a stable fat emulsion consisting of palm oil and oat oil that can reduce food intake and Overweight and obesity have become a global epi- enhance satiety , although not all such studies demic, associated with significant increases in mor- have yielded significant effects . Long-term tality and the risk of many chronic disorders, such as observations have confirmed the physiological activ- diabetes mellitus, hypertension, heart disease, and ity of this fat emulsion on parameters relevant to other adverse health events [1,2].
actual weight management, regarded also as target Affordable and effective weight management stra- functions for health benefits including maintenance tegies are needed. Using data from national surveys, of body-weight, decreased body fat mass, and it was estimated that by affecting an energy balance by reduced waist circumference after weight loss [9,10].
100 kilocalories per day (e.g. 4% of daily energy The mechanism by which this stable fat emulsion intake), weight gain in most of the US population exerts these short- and long-term effects has so could be prevented . It is in this context that far been unclear, although it has been suggested ingredients designed to affect the mechanism regulat- that the ‘‘ileal brake'' mechanism utilizes feedback ing satiety may play a role, especially if these could signals resulting in a decrease in gastrointestinal be incorporated into everyday foods.
transit time. Under normal physiological conditions, Correspondence: Arvo Haenni, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Clinical Trials, P.O. Box 609, UppsalaUniversity, SE-751 25 Uppsala, Sweden. Tel: 46 18 6117 195. Fax: 46 18 137 342. E-mail: [email protected] (Received 17 April 2009; accepted 20 June 2009) ISSN 0036-5521 print/ISSN 1502-7708 online # 2009 Informa UK Ltd.
DOI: 10.1080/00365520903131999 Stable fat emulsion and orocecal transit time undigested fatty acids reaching the ileum activate the Unauthorized use 8.5 ed. stable emulsion palm oil and oat oil ‘‘ileal break'' , which is associated with the slowing down of gastrointestinal transit time, release The subjects were served a meal at 1100 h of satiety hormones, and induction of satiety . In consisting of a 400 ml nutritional drink (800 kcal order to demonstrate activation of the ileal brake Energy% C/F/P 51/13/36; Na¨ringsdryck, Novartis, mechanism, we investigated a of this stable single copy fo Sweden) onal the addition of 1000 mg salazopyrine.
fat emulsion consumption on orocecal transit time in The afternoon meal was served at 1500 h, during healthy, normal-weight men.
which, again, a nutritional drink (800 kcal) wasserved without salazopyrine. The evening meal wasserved at 1900 h and consisted of 600 g hash (900 Material and methods kcal Energy% C/F/P 50/38/12; Oxpytt, Findus, The total amount of energy during the test day The subjects were recruited by advertising in the was 2750 kcal/day and the subjects were instructed local papers. Subjects were eligible for the trial if to consume everything they were offered.
they met the following inclusion criteria: malegender, aged 2070 years, body mass index (BMI)2228 kg/m2, and regular evacuation habits. The following criteria were used to exclude subjects: For this study, two yoghurt products were made and contraindications to salazopyrine treatment, history investigated, the control yoghurt containing milk fat of allergy or asthma, consumption of more than and the active product containing the stable fat three cups of coffee per day, restrained eating, emulsion (Fabuless; DSM Food Specialties, Delft, abnormal blood safety parameters, hypertension The Netherlands). The two compositions had iden- (systolic blood pressure ]140 mmHg or diastolic tical appearance and had the same faintly vanilla-like blood pressure ]85 mmHg), and concomitant med- ication. All routine blood safety parameters werechecked at the Department of Clinical Chemistry,Uppsala University Hospital.
Yoghurt with dairy fat After initial screening by telephone, 25 subjects A mixture of commercial, full-fat milk and skimmed attended the screening visit, after which15 subjects milk (6:1) was pasteurized for 35 min at 83.58C, were found eligible for randomization. The study cooled down to 158C, and stored overnight. The protocol was approved by the local ethics committee temperature was set at 438C and 176 ml/l of the at the Faculty of Medicine at Uppsala University.
starter culture CY222 (DSM Food Specialties) was Each participant gave informed consent.
added. After about 4.5 h the pH was below 4.6 andthe yoghurt was homogenized at 150 bar using a Rannie lab homogenizer (Model APV 1000; APVHomogenizers AS, Albertslund, Denmark). The The study was of randomized, double-blind, con- cream flavoring (540040H, Givaudan) was stirred trolled, cross-over design and was carried out within into the yoghurt (0.1 g/l).
2 weeks. Each subject was studied on two occasions,on the same day of each week, and with a 1-weekinterval between the cross-over.
The day before the test day the subjects received This was made by preparing a 42.5 wt% emulsion all food items to be consumed. The energy and with purified palm oil (40.0%) and fractionated oat macronutrient level was set according to the Swedish oil (2.5%) in water (57.5%).
Nutrition Recommendations (SNR) for men at2050 Yoghurt with Fabuless fat (2750 Kcal; Energy% C/F/P 55/30/15).
The subjects arrived at the study site in the Commercial skimmed milk (1120 g) (Albert Heijn, morning in fasted state and received a yoghurt The Netherlands) was heated to 458C using a breakfast at 0800 h. The compositions of both microwave oven. Fabuless (DSM Food Specialties, yoghurts were matched for energy and macronutri- batch KLB06027) was heated to about 358C and ents (238 kcal Energy% C/F/P 49/20/31 for the 80 g was carefully added to the milk. This mixture active product and 244 kcal, Energy% C/F/P 48/ was homogenized with the Flashblend Liquid Mixer 21/31 for the control). However the control yoghurt L4RT (Silverson Machines Inc., East Longmeadow, contained only milk fat, while in the test yoghurt Mass., USA) at 900 rpm for 10 min. The pasteur- (active treatment) 8.5 g milk fat was replaced by izations and the rest of the processes were the same A. Haenni et al.
as those for the yoghurt with dairy fat. The mean particle size was 589/520 nm with 13.8/11.7% Data are reported as the mean9standard deviation and nt meal on sulfapyr- idine absorption was analyzed by calculating the change in sulfapyridine absorption in both treatment groups (D: controlactive). These differences were Body-weight was measured using a digital balance calculated from time-point 0 h until 11 h; the total (CL-300 BMI; Carl Liden, Gothenburg, Sweden) period was split into two phases, 14 h and 511 h.
with subjects wearing indoor clothes but without The data evolution throughout the follow-up was shoes, wallet, and keys. Height was measured using a studied using the analysis of variance for repeated wall-mounted stadiometer at the screening visit.
measurements (ANOVA) (Univariate Mixed Effect BMI was calculated by dividing body-weight mass Model Approach). Statistical ANOVA was done (kg) by body height squared (m2). Blood pressure using SAS software (SAS Institute, Cary, N.C., and pulse rate were measured oscillometrically USA). A p-value of less than 0.05 was considered (Omron M4-I; Omron Healthcare Europe B.V., to be statistically significant.
Hoofddorp, The Netherlands) in the right arm, insitting position, after a rest period of 35 min.
Orocecal time determination The baseline characteristics of the study populationare presented in Table I.
Salazopyrine was used as a marker for orocecal The sulfapyridine concentrations in serum after transit time . Salazopyrine is poorly absorbed receiving products with stable fat emulsion or in the gastrointestinal tract when administered orally, but after being hydrolyzed by the flora of across these two treatments (Table II). During the the colon it is rapidly absorbed as sulfapyridine and first 4 h, sulfapyridine serum levels in both treat- 5-aminosalicylic acid . Blood samples were ments were close to detection level and not withdrawn before the lunch meal and every hour until 11 h after the meal for determination of ANOVArepeated measurement; p0.91).
sulfapyridine in the serum. The samples were kept However, between 4 and 5 h, serum sulfapyridine for 2030 min at room temperature before centrifu- levels increased significantly in the control treatment gation for 12 min at 3600 rpm. The serum was group (0.6 mmol/l to 2.6 mmol/l (p B0.05)) compared transferred to cryo-tubes and stored at 208C until to the active treatment group (active; 0.5 mmol/l to the analysis was undertaken at the laboratory forclinical chemistry at Uddevalla Hospital, Sweden.
Table I. General characteristics of the study population (n 15),all male.
Sulfapyridine concentration in serum was ana- lyzed according to a method described by Hansson et al. using the enzymatic hydrolysis of the serum samples . The detection level of sulfapyridine in serum is 0.3 mmol/l.
Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) B-hemoglobin, (g/l) Safety assessments B-erythrocytes, (1012/l) A safety assessment at the last visit, including blood B-leukocytes, (1012/l) sampling and physical examination, was carried out B-thrombocytes, (1012/l) because of the salazopyrine given during the trial.
P-bilirubin, (mmol/l) Sample size assessment Study group sizes were determined to detect a P-creatinine, (mkat/l) difference of 60 min between the active and the control group, with a power of 80% and a standarddeviation (SD) of 1.20 and a type I error of 5%, and Abbreviations: BMI body mass index; ALAT alanine amino-transferase; ASAT aspartate aminotransferase; ALP alkaline a sample size of 14 subjects. When adjusted for phosphatase; GGT gamma-glutamyl transferase; TSH thyr- dropouts during the study, the total number of subjects included at visit 1 should be 15.
Data are expressed as the mean9SD.
Stable fat emulsion and orocecal transit time Table II. Comparison of the sulphapyridine concentrations in serum (mmol/l) after receiving active and control yoghurt.
print a single B0.3 Data are expressed as the mean9SD.
1Detection limit is B0.3; ANOVA-repeated measurement p-values presented are for the time-point 0 to 4 h, and 5 to 11 h, respectively.
1.1 mmol/l; (p B0.05) Table II). After the initial delay heterogeneity between the study results was found.
in the appearance of sulfapyridine in the blood- Short- and long-term effects on feelings of hunger stream, the absorption curves showed similar ki- and the satiety hormone GLP-1 were also observed netics in the two different regimens, as displayed in [46,9]. During long-term studies of 34 months, Figure 1. By extrapolating the curves of the serum consumption of this stable fat emulsion improved levels to the x-axis, a difference was obtained maintenance of body-weight and reduced body fat corresponding to a 45-min increase in transit time mass after an initial weight loss [9,10]. These effects in the treatment containing the stable fat emulsion.
have been observed using this stable fat emulsion in No adverse events were registered during the different food matrices, including dairy-based pro- study visits or at the follow-up visit. All participants ducts and meal replacers.
completed the study.
The underlying mechanism of action is so far not understood, though it has been suggested that theobservations could be explained by activation of the ‘‘ileal brake'' mechanism.
Short-term studies have shown that the stable fat This study was designed to investigate the effect of emulsion Fabuless can have significant appetite- the fat emulsion on one of the characteristics of the suppressant effects compared to the control at ‘‘ileal brake'', the orocecal transit time of a meal, as approx. 4, 8, and 36 h post-treatment, although analyzed by a non-invasive method using salazopyr-ine as a marker for arrival of food in the colon. Theappearance of sulfapyridine, a metabolite formedfrom salazopyrine in the colon, was determined. Astatistically significant difference in sulfapyridineappearance in the plasma was observed whencomparing active versus control products. Thisdifference corresponds to a 45-min increase intransit time.
It has previously been shown, that the presence of fat in the distal ileum leads to a slowing down of thetransit time from ingestion to colon, stimulates therelease of gastrointestinal hormones, inhibits pan-creaticobiliary and gastric acid secretion, and sup-presses appetite and energy intake as a result of thedigestion of fats into free fatty acids [11,13,2025].
The increase in orocecal transit time obtained inthis study is in line with results obtained in astudy with lipid infusions into the ileum, also Figure 1. Comparing orocecal transit time (by measuring the level showing an increase in gastrointestinal transit time of sulfapyridine) in both treatment groups: active and control.
Values are expressed as means; p B0.05 over time difference from of about 45 min . Notably, the activation of the baseline compared to 12 h (repeated measurement ANOVA).
feed-back mechanism occurred about 3 h after A. Haenni et al.
consumption of Fabuless. This is in accordance with  Read NW, McFarlane A, Kinsman RI, Bates TE, Blackhall earlier observations showing a significant reduction NW, Farrar GB, et al. Effect of infusion of nutrient solutionsinto the ileum on gastrointestinal transit and plasma levels of in energy intake 4 h after Fabuless consumption .
view and . Gastroenterology 1984;/ The effect of this palm/oat oil emulsion on gastrointestinal transit time may be appreciated as  Spiller RC, Trotman IF, Higgins BE, Ghatei MA, Grimble a physiologically relevant print a related The ileal brake: inhibition of jejunal mechanisms involved in appetite control. The pre- motility after ileal fat perfusion in man. Gut 1984;25: sent observations could indicate that regulation of  Maljaars PW, Peters HP, Mela DJ, Masclee AA. Ileal brake: transit time may be a mechanism underlying the a sensible food target for appetite control [review]. Physiol effects observed with this emulsion.
 Van Citters GW, Lin HC. The ileal brake: a fifteen-year Declaration of interests: The authors report no progress report. Curr Gastroenterol Rep 1999;1:4049.
 Gramatte T, Terhaag B. The variability of orocecal transit conflicts of interest. The authors alone are respon- time evaluated by the salicylazosulphapyridine/sulphapyri- sible for the content and writing of the paper.
dine method. Int J Clin Pharmacol Ther Toxicol 1991;29:  Sogni P, Chaussade S, Akue-Gohe K, Nepveux P, Homerin M, Couturier D, et al. Comparative effects of ricinoleic acid and senna on orocecal and oroanal transit time in healthy  Allison DB, Fontaine KR, Manson JE, Stevens J, VanItallie subjects. Application of the salacylazosulfapyridine method.
TB. Annual deaths attributable to obesity in the United Gastroenterol Clin Biol 1992;16:214.
States. JAMA 1999;282:15308.
 Sunesen VH, Vedelsdal R, Kristensen HG, Christrup L,  World Health Organization (WHO). Obesity: preventing and Mullertz A. Effect of liquid volume and food intake on the managing the global epidemic, report of a WHO consulta- absolute bioavailability of danazol, a poorly soluble drug.
tion on obesity, WHO: Geneva: WHO/NUD/NCD/98.1; Eur J Pharm Sci 2005;24:297303.
 Kellow JE, Borody TJ, Phillips SF, Haddad AC, Brown ML.
 Hill JO, Wyatt HR, Reed GW, Peters JC. Obesity and the Sulfapyridine appearance in plasma after salicylazosulfapyr- environment: where do we go from here? Science 2003;299: idine. Another simple measure of intestinal transit. Gastro-  Burns AA, Livingstone MB, Welch RW, Dunne A, Robson  Hansson KA, Sandberg M. Determination of sulphapyridine PJ, Lindmark L, et al. Short-term effects of yoghurt contain- and its metabolites in biological materials after administra- ing a novel fat emulsion on energy and macronutrient intakes tion of salicylazosulphapyridine. Acta Pharm Suec 1973;10: in non-obese subjects. Int J Obes Relat Metab Disord 2000;  Welch I, Saunders K, Read NW. Effect of ileal and  Burns AA, Livingstone MB, Welch RW, Dunne A, Reid CA, intravenous infusions of fat emulsions on feeding and satiety Rowland IR. The effects of yoghurt containing a novel fat in human volunteers. Gastroenterology 1985;89:12937.
emulsion on energy and macronutrient intakes in non-  Welch IM, Davison PA, Worlding J, Read NW. Effect of ileal overweight, overweight and obese subjects. Int J Obes Relat infusion of lipid on jejunal motor patterns after a nutrient Metab Disord 2001;25:148796.
and nonnutrient meal. Am J Physiol 1988;255:G8006.
 Layer P, Holst JJ, Grandt D, Goebell H. Ileal release of Rowland IR. Dose-response effects of a novel fat emulsion glucagon-like peptide-1 (GLP-1). Association with inhibi- (Olibra) on energy and macronutrient intakes up to 36 h tion of gastric acid secretion in humans. Dig Dis Sci 1995;/ post-consumption. Eur J Clin Nutr 2002;56:36877.
 Diepvens K, Steijns J, Zuurendonk P. Westerterp-Plantenga  Holgate AM, Read NW. Effect of ileal infusion of intralipid MS. Short-term effects of a novel fat emulsion on appetite on gastrointestinal transit, ileal flow rate, and carbohydrate and food intake. Physiol Behav 2008;95:1147.
absorption in humans after ingestion of a liquid meal.
 Logan CM, McCaffrey TA, Wallace JM, Robson PJ, Welch RW, Dunne A, et al. Investigation of the medium-term  Keller J, Holst JJ, Layer P. Inhibition of human pancreatic effects of Olibratrade mark fat emulsion on food intake in and biliary output but not intestinal motility by physiological non-obese subjects. Eur J Clin Nutr 2006;60:108191.
intraileal lipid loads. Am J Physiol Gastrointest Liver Physiol  Diepvens K, Soenen S, Steijns J, Arnold M, Westerterp- Plantenga M. Long-term effects of consumption of a novel  Symersky T, Kee B, Haddeman E, Peters HP, Masclee AA.
fat emulsion in relation to body-weight management. Int J Low dose ileal oil perfusion increases satiety in humans.
Obes (Lond) 2007;31:9429.
Gastroenterology 2004;126(A60): Suppl 2.
 Olsson J, Sundberg B, Olsson R, Viberg A, Yazdanpanah N,  Maljaars J, Symersky T, Kee BC, Haddeman E, Peters HP, Haenni A. Effect of fat emulsion on body composition; a 12- Masclee AA. Effect of ileal fat perfusion on satiety and week study in overweight women on a meal replacement hormone release in healthy volunteers. Int J Obes 2008;32: therapy after an initial weight loss. 2009; to be submitted.
Blackwell Publishing Asia Evaluation of radioiodinated vesamicol analogs for sigma receptor imaging in tumor and radionuclide receptor therapy Kazuma Ogawa,1,2,5 Kazuhiro Shiba,2 Nasima Akhter,3 Mitsuyoshi Yoshimoto,3 Kohshin Washiyama,3 Seigo Kinuya,3 Keiichi Kawai3,4 and Hirofumi Mori2 1Graduate School of Natural Science and Technology, 2Advanced Science Research Center, 3Graduate School of Medical Sciences, Kanazawa University, Kanazawa; 4Biomedical Imaging Research Center, University of Fukui, Fukui, Japan
ASCO SPECIAL ARTICLE Recommendations for the Use of Antiemetics: Evidence-Based, Clinical Practice Guidelines By Richard J. Gralla, David Osoba, Mark G. Kris, Peter Kirkbride, Paul J. Hesketh, Lawrence W. Chinnery, Rebecca Clark-Snow, David P. Gill, Susan Groshen, Steven Grunberg, James M. Koeller, Gary R. Morrow, Edith A. Perez, Jeffrey H. Silber, and David G. Pfister for the American Society of Clinical Oncology