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Keywords:

  • Food intake;
  • meta-analysis;
  • meta-regression;
  • vegetable oil emulsion

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflicts of Interest Statement
  9. Acknowledgements
  10. References

Several short-term studies have investigated the effects of a vegetable oil emulsion on subsequent food intake, although findings have been inconsistent. This work aimed to review all studies, and investigate differences in study outcomes based on methodology. All known studies were identified. Data were abstracted from published studies (n = 7). Details of unpublished studies were gained from investigators/sponsors (n = 5), or were unavailable for reasons of confidentiality (n = 4). Available data were combined using meta-analyses. A combined appetite suppressant effect of the emulsion compared with control was found for test meal intake at approximately 4, 12 and 36 h post-treatment: smallest combined mean difference (random effects model) = 0.53 MJ (95% confidence interval 0.20, 0.86), P < 0.01. However, considerable heterogeneity (variability) between study results was also found (smallest I2 = 94%, P < 0.01), questioning the predictive validity of the above findings. Meta-regression suggested this heterogeneity to be related to differences in the processed nature of the product, treatment dose and in particular year of study (smallest B = 0.54, 95% confidence interval 0.06, 1.03, P = 0.04), although again heterogeneity was found. The only consistent finding was a lack of effect on food intake 4 h post-preload in studies conducted after 2003. These results suggest a small but inconsistent appetite suppressant effect of the vegetable oil emulsion. However, due to the large heterogeneity, no definitive conclusions can be drawn.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflicts of Interest Statement
  9. Acknowledgements
  10. References

The prevalence of overweight and obesity continues to increase throughout the world (1). Alongside this increase, the health costs and implications associated with obesity also continue to rise (2). These rising health costs and implications highlight the need for strategies and aids to treat and prevent weight gain.

Industry has responded to this growing need with the development and manufacture of various products aiming to aid weight loss and promote weight management. One such product is a novel vegetable oil emulsion (Fabuless™[previously Olibra®]), formulated from palm oil and oat oil fractions, demonstrated to prolong the passage of foods through the small intestine (3), potentially resulting in increased and extended post-prandial satiety.

The effects of this vegetable oil emulsion on appetite have been investigated repeatedly. Early studies report a suppression of appetite (reduction in food intake and hunger ratings) after a single dose of this oil emulsion compared with control. Burns et al. (4) found that the oil emulsion reduced test meal intake, Burns et al. (5) found that the emulsion reduced both test meal intake and rated hunger for up to 24 h, and Burns et al. (6) reported reduced test meal intake up to 36 h following the oil emulsion. Other studies, however, have failed to find effects. Logan et al. (7) found no effects compared with control on three separate test days during a 21-day consumption period, and Rogers and colleagues at the University of Bristol found no effects of the oil emulsion in several currently unpublished studies.

Short-term laboratory-based studies of acute appetite effects have the advantage of a high degree of control over extraneous variables and accurate measurement of food intake. However, in relation to the assessment of food ingredients as potential aids to weight management, they are limited by the short time frame over which effects are measured, the artificial nature of the situations involved, and the assumption that weight management is achieved only through changes in appetite (8,9).

Differences between short-term study outcomes may occur as a result of differences in study methodology. Explanation of these differences may increase understanding of the potential value of this oil emulsion to aid weight management. This paper reviews all studies investigating the effects of the vegetable oil emulsion on appetite and food intake, and investigates explanations for differences between study outcomes based on study methodology.

Methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflicts of Interest Statement
  9. Acknowledgements
  10. References

Review of studies

All studies investigating the effects of the vegetable oil emulsion (Fabuless™, DSM Nutritional Products, Switzerland, formerly also known as Olibra®) on appetite and food intake were identified. Published studies were obtained from relevant journals. Data on the methodology of all published studies were abstracted independently by two researchers, and discordances were resolved by a third researcher. Investigators and sponsors of all unpublished studies were contacted and data were requested. Where investigators and sponsors agreed to the use of data, required details were provided.

Analysis of studies

The methods and findings of all available studies were reviewed. All aspects of methods thought to be important in appetite research, as judged by the authors, contributors from DSM, and as published (8–10), were considered. Data from all available studies were subsequently combined using meta-analysis. Both random and fixed effects models were used to estimate combined mean differences, although random effects models are theoretically preferable when combining the results of studies when heterogeneity exists (11–13). Heterogeneity was investigated using Higgins' I2 statistic (14,15), which describes the proportion of total variation in study estimates that is due to heterogeneity. Meta-regressions were conducted to explore possible sources of heterogeneity. Sensitivity analyses were subsequently conducted where possible sources of heterogeneity were identified. For all sensitivity analyses, effects were investigated by dividing available studies into two approximately equal groups and comparing effects in each separate group. Analyses were performed in Stata Version 8.1 (StataCorp. Stata Statistical Software: Release 8.0. College Station, TX: Stata Corporation, 2003), using the ‘meta’ and ‘metareg’ commands.

Results

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflicts of Interest Statement
  9. Acknowledgements
  10. References

Sixteen studies investigating effects on appetite and food intake were identified. Seven of these studies have been published (Burns et al. (4)– studies 1 and 2; Burns et al. (5); Burns et al. (6); Logan et al. (7); Diepvens et al. (16); Smit et al. (17)), and nine studies are unpublished. All published studies were obtained and are included in the review and analysis. Of those that are currently unpublished, full methods and data were obtained from investigators and sponsors for five studies (studies BF, U1, U3, U4, DSM), but neither methods nor data could be obtained for four studies, for reasons of confidentiality.

The methods of all studies for which methodological details were available are shown in Table 1. Studies were conducted between roughly 1998 and 2006 at the University of Ulster, the Unilever Health Institute, Vlaardingen, the University of Bristol and the University of Maastricht. All studies used a single or double blind, placebo-controlled within-subjects design, with a preloading procedure, in which participants experienced the treatment as a preload and appetite was subsequently measured over the short term. In all studies, appetite was measured using food intake and subjective ratings, excepting one (study U1) where only subjective ratings were used. All participants experienced each treatment only once, with the exception of the study by Logan et al. (7), where participants experienced the treatment up to 21 times. Male and female participants were involved in all studies, although in differing proportions, excepting in one study (16) where only female participants were used. The majority of studies involved participants with a mean age of approximately 25 years, although in two studies, mean age was approximately 30 years (5 [overweight group], 7), and in three studies, mean age was approximately 40 years (5 [obese group]; 16 [older group]; study U1). Studies involved lean (4, studies 1 and 2, 5–7, 16, 17, studies BF, U3, U4, DSM), overweight (4, study 2, 5, 16, study U1), and obese participants (5). The majority of studies also involved only non-smokers, non-vegetarians and participants low in dietary restraint (5, 16, 17, studies BF, U3, U4, DSM), although other selection criteria differed between studies.

Table 1.  Review of methodology and results for all studies as published
Study  Design     
NamePlaceStudy yearWS/BS, single/double blind, placebo controlExperience of treatmentSexAgeBMIOther exclusion criteria
Range, meanRange, mean
Burns et al. (4), Study 1University of Ulster, UK1998*Double blind, placebo control, WS crossover, Preloading procedure1 dose15 F, 14 M18–65, F = 23, M = 24≤30, F = 22, M = 22Non-smokers, not taking appetite affecting medication
Burns et al. (4), Study 2University of Ulster, UK1998*Double blind, placebo control, WS crossover, Preloading procedure1 dose16 F, 14 M18–65, F = 25, M = 26≤30, F = 22, M = 25Non-smokers, not taking appetite affecting medication
Burns et al. (5)University of Ulster, UK1999*Double blind, placebo control, WS crossover, Preloading procedure1 dose33 F, 27 M, A: 10 F, 10 M; B: 10 F, 10 M; C: 13 F, 7 M.18–65, A: F = 25, M = 30; B: F = 33, M = 32; C: F = 41; M = 38A: 20–24.9, F = 22, M = 23; B: 25–29.9, F = 27, M = 26; C: 30+, F = 34, M = 32Non-smokers, not taking appetite affecting medication
Burns et al. (6)University of Ulster, UK2000*Single blind, placebo control, WS crossover, Preloading procedure1 dose30 F, 20 M18–65, F = 24, M = 2720–25, F = 22, M = 24Non-smokers, not taking appetite affecting medication, DEBQR non-restrained
Study BFUnknown2000Single blind, placebo control, WS crossover, Preloading procedure1 dose19 F, 15 MF = 22, M = 22F = 22, M = 24Non-smokers, not taking appetite affecting medication
Logan et al. (7)University of Ulster, UK2004*Double blind, placebo control, WS crossover, Preloading procedure, repeated measures22 doses, testing for doses 1, 8, 2214 F, 14 M20–55, F = 29, M = 31<30, F = 23, M = 23Non-smokers, not taking appetite affecting medication, normal blood lipids
Diepvens et al. (16)Maastricht University, NL2004Double blind, placebo control, WS crossover, Preloading procedure1 dose41 F, A:21 F, B:20 FA: 24 B: 44A: 22 B: 28In good health, unrestrained eaters (TFEQ), stable body weight
Study U1Unilever Health Institute, NL2005Double blind, placebo control, WS crossover, Preloading procedure1 dose12 F, 6 M24–59, F = 33, M = 4322.4–33.8, F = 25, M = 25
Smit et al. (17)University of Bristol, UK2005Double blind, placebo control, WS crossover; Preloading procedure1 dose16 F, 8 M18–43, Mean = 2318–37, Mean = 22Non-smokers, not taking appetite affecting medication, not dieting, otherwise healthy.
Study U3University of Bristol, UK2005Double blind, placebo control, WS crossover, Preloading procedure1 dose16 F, 8 M18–55, Mean = 2521–32, Mean = 22Non-smokers, not taking appetite affecting medication, not dieting, otherwise healthy.
Study U4University of Bristol, UK2006Double blind, placebo control, WS crossover, Preloading procedure1 dose16 F, 8 M20–55, Mean=2721–32, Mean = 24Non-smokers, not taking appetite affecting medication, not dieting, otherwise healthy.
DSMUniversity of Bristol, UK2006Double blind, placebo control, WS crossover, Preloading procedure1 dose17 F, 19 M20–60, Mean = 2421–32, Mean = 23Non-smokers, not taking appetite affecting medication, not dieting, otherwise healthy.
StudyPreload   Food intake (4 h post-preload)   
NameDose: g macronutrients, g fats.VehicleTimeVASTest meal foods, Inc. familiarity, presentation and selection of foods.Test meal settingTest meal timeTest meal duration
Processed Fabuless used unless otherwise stated
Burns et al. (4), Study 1800 kJ: 6.8 g prot., 1 g milk fat, 28.8 g carb, +Yoghurt 200 g13:00PleasantnessBuffet, 36 familiar foods, sweet & savoury, hot & cold, ad-lib portions, self-selection,Metabolic suite dining area17:00Unlimited
T – 12.5 g Fabuless emulsion (5 g Fabuless fats).
P – 5 g milk fat.
Burns et al. (4), Study 2800 kJ, 6.8 g prot., 1 g milk fat, 28.8 g carb, +Yoghurt 200 g13:00PleasantnessBuffet, 36 familiar foods, sweet & savoury, hot & cold, ad-lib portions, self-selection,Metabolic suite dining area17:00Unlimited
T – 12.5 g Fabuless emulsion (5 g Fabuless fats).
P – 5 g milk fat.
Burns et al. (5)800 kJ, 6.8 g prot., 1 g milk fat, 28.8 g carb, +Yoghurt 200 g9:00PleasantnessBuffet, 23 familiar foods, sweet & savoury, hot & cold, ad-lib portions, self-selection,Metabolic suite dining area13:00Unlimited
T – 12.5 g Fabuless emulsion (5 g Fabuless fats).
P – 5 g milk fat.
Burns et al. (6)1165 kJ, 6.8 g prot., 10 g milk fat, 28.8 g carb, +Yoghurt 200 g9:00PleasantnessBuffet, 17 familiar foods, sweet & savoury, hot & cold, ad-lib portions, self-selection,Metabolic suite dining area13:00Unlimited
T1 (unpublished data) – 13 g milk fat, 2 g unprocessed Fabuless emulsion (0.8 g Fabuless fats)
T2 – 10 g milk fat, 5 g unprocessed Fabuless emulsion (2 g Fabuless fats). T3 – 5 g milk fat, 10 g unprocessed Fabuless emulsion (4 g Fabuless fats).
T4 – 15 g unprocessed Fabuless emulsion (6 g Fabuless fats).
P – 15 g milk fat.
Study BF377.5 kJ, 1.875 g prot., 12 g carb. +Soup 250 g13:00PleasantnessBuffet, 22 familiar foods, sweet & savoury, hot & cold, ad-lib portions, self-selection,Metabolic suite dining area17:00Unlimited
T1 – 10 g unprocessed Fabuless emulsion (4 g Fabuless fats)
T2 – 10 g processed Fabuless emulsion (4 g Fabuless fats)
P – 10 g fats
Logan et al. (7)760 kJ, 6 g prot., 28 g carb. +Yoghurt 200 g9:00PleasantnessBuffet, 43 familiar foods and drinks, sweet & savoury, hot & coldMetabolic suite dining area13:00Unlimited
T1, 8, 22 – 5 g Fabuless fat (12.5 g Fabuless emulsion).
P1, 8, 22 – 5 g fat.
Diepvens et al. (16)900 kJ, 7.5 g prot., 39 g carb. +Yoghurt 250 g8:00Palatability.Lasagna (tomato sauce and minced meat), water, ad-lib portions, self-selection13:0020 min max
T – 4.2 g fat inc. 10 g Fabuless emulsion (4 g Fabuless fats)
P – 4.2 g milk fat
Study U1920 kJ, 10 g prot., 3 g fat, 30 g carb. +Milk-based ready-to-drink shake 344 g/325 mL12:00Sweetness, palatability, fatness, after-taste, granularityNot measuredN/AN/AN/A
T – 6 g Fabuless emulsion (2.5 g Fabuless fats)
P – 6 g vegetable cream (2 g fat)
Smit et al. (17)1113 kJ, 15.2 g prot., 4 g fibre, 38 g carb. +Yoghurt drink 336 g/325 mL9:00Pleasantness: overall, mouthfeel/texture, flavour, aroma.Buffet, cheese sandwiches, custard cream biscuits and water, ad-lib portions, self-selectionIndividual testing booth13:0030 min max
T1 – 5.7 g fat inc. 5.0 g Fabuless fat (12.5 g Fabuless emulsion).
T2 – 5.7 g fat inc. 5.0 g unprocessed Fabuless fat (12.5 g Fabuless emulsion).
P – 5.8 g milk fat.
Study U3T1 – 5 g Fabuless emulsion (2.0 g Fabuless fat)‘shot drink’ 100 mL10:30Pleasantness: overall, mouth-feel/texture, flavour, aroma.Buffet, cheese sandwiches, crisps, yoghurt and water, ad-lib portions, self-selectionIndividual testing booth13:3030 min max
T2 – 8 g Fabuless emulsion (3.2 g Fabuless fat)
P1 – 2.0 g milk fat
P2 – 3.2 g milk fat
Study U4T – 12.5 g Fabuless (5 g Fabuless fat)‘mini-drink’ 100 mL9:00Pleasantness: overall, mouth-feel/texture, flavour, aroma.Buffet, cheese sandwiches, custard cream biscuits, fruit, water; ad-lib portions (fruit taken and eaten first), self-selectionIndividual testing booth13:0030 min max
P – 5 g milk fat
DSMT – 12.5 g Fabuless emulsion (5 g Fabuless fat) + 1 g milk fatYoghurt 200 mL9:00Pleasantness: overall, mouth-feel/texture, flavour, aroma.Buffet, 17 familiar foods & drinks, sweet & savoury, cold, ad-lib portions, self-selectionIndividual testing booth13:0030 min max
P – 6 g of milk fat
StudyFood intake (8 h)    Appetite Other
NameTest meal foodsTest meal settingTest meal timeTest meal durationSubsequent intakeVASTimeVAS
Burns et al. (4), Study 1N/AN/AN/AN/ANatural, recorded in weighed food diaries for rest of dayHunger, desire to eat, preoccupation with thoughts of foodPre-/post-preload, hourly – 17:00Ill effects, discomfort
Burns et al. (4), Study 2N/AN/AN/AN/ANatural, recorded in weighed food diaries for rest of dayHunger, desire to eat, preoccupation with thoughts of foodPre-/post-preload, hourly – 17:00Ill effects, discomfort
Burns et al. (5)Buffet, 36 familiar foods, sweet & savoury, hot & cold, ad-lib portions, self-selection,Metabolic suite dining area17:00UnlimitedNatural, recorded in weighed food diaries for rest of day, and following day to 21:00Hunger, desire to eat, preoccupation with thoughts of food, perceived fullness, thirstPre-/post-preload, hourly – 21:00Ill effects, discomfort
Burns et al. (6)N/AN/AN/AN/ANatural, recorded in weighed food diaries for rest of day, and following day to 21:00Hunger, desire to eat, fullness,Pre-/post-preload, hourly – 21:00Ill effects, discomfort
Study BFN/AN/AN/AN/ANatural, recorded in weighed food diaries for rest of dayHunger, desire to eat, preoccupation with thoughts of food, fullnessBreakfast – 13:00 hourly, 13:00–17:00 half-hourly, 17:00–21:00 hourlyIll effects, discomfort
Logan et al. (7)N/AN/AN/AN/ANatural, recorded in weighed food diaries for rest of day, and following day to 21:00Hunger, fullness, desire to eat, amount they could eat, preoccupation with thoughts of foodPre-/15 min post-preload, hourly – 21:00
Diepvens et al. (16)N/AN/AN/AN/AN/AHunger, desire to eat, fullness, prospective consumptionPre-/post-breakfast preload, hourly −16:00.
Study U1N/AN/AN/AN/ANatural after 17:30. Recorded time, meal or snack, and if more or less than usual.Appetite for a meal, satiety/fullness, hunger, appetite for snackPre-/post-preload, hourly – 17:30Nausea, stomach complaints
Smit et al. (17)Buffet, pasta dish, yoghurt, water, ad-lib portions, self-selection.Individual testing booth17:0030 min maxSnacks (provided snacks only) & drinks allowed for rest of day from 19:00, recorded unweighed in food diariesAmount they could eat, fullness, hunger, appetite for snack, thirst, satiation, energy, drained.Pre-/post-breakfast-preload, half-hourly – 17:30.Adverse physical symptoms
Study U3Buffet, pasta dish, bread rolls, swiss roll, water, ad-lib portions, self-selection.Individual testing booth17:3030 min maxSnacks (provided snacks only) & drinks allowed for rest of day from 19:00, recorded unweighed in food diariesAppetite for a meal, amount they could eat, fullness, hunger, appetite for snack, thirst, satiation, energy, drained.Pre-/post-breakfast, half-hourly – 18:00.Gastro-intestinal complaints
Study U4Buffet, salad, pasta dish, bread rolls, swiss roll, water, ad-lib portions (salad accepted and eaten first), self-selection.Individual testing booth17:0030 min maxSnacks (provided snacks only) & drinks allowed for rest of day from 19:00–23:00, recorded unweighed in food diariesHunger, fullness, desire to eat, occupied by thoughts of foodPre-/post-breakfast preload, half-hourly −17:30.Gastro-intestinal complaints
DSMBuffet, 14 familiar foods & drinks, sweet & savoury, hot & cold, ad-lib portions, self-selectionIndividual testing booth17:0030 min maxSnacks (provided snacks only) & drinks allowed for rest of day from 19:00–23:00, recorded unweighed in food diariesHunger, fullness, desire to eat, occupied by thoughts of foodPre-/post-breakfast preload, half-hourly −17:30.Gastro-intestinal complaints
Study   
NameProcedural controlsFood beforeActivity beforeTime between treatments
Burns et al. (4), Study 1Fasting from 20:00 previous dayStandard breakfast providedNo moderate – heavy exercise1 week
(25% estimated energy expenditure)
Burns et al. (4), Study 2Fasting from 20:00 previous dayStandard breakfast providedNo moderate – heavy exercise1 week
(25% estimated energy expenditure)
Burns et al. (5)Fasting from 20:00 previous dayFastedNo moderate – heavy exercise1 week
Burns et al. (6)Fasting after evening meal from 20:00Standard evening meal provided at 18:00No moderate – heavy exercise1 week
Study BFFasting from 20:00 previous dayStandard breakfast providedNo moderate – heavy exercise1 week
(25% estimated energy expenditure)
Logan et al. (7)Fasting from 21:00Fasted3 weeks
Diepvens et al. (16)Fasting from 22:00.FastedNo moderate – heavy exercise1 week
Study U1Standard breakfast at home before 9:00, ad-lib tea/coffee, fasting from 11:002 days
Smit et al. (17)Fasting from 20:00.FastedNo exerciseMinimum of 72 h
Study U3Fasting from 23:00. Fasting from alcohol and high-fibre foods from 18:00Standard breakfast provided at 8.30No moderate-heavy exercise1 week
Study U4Fasting from 23:00. Fasting from alcohol and high-fibre foods all day. All activities, food & drinks recorded in diaries.Standard breakfast provided at 8.30No moderate-heavy exercise1 week
DSMFasting from 20:00. Fasting from alcohol all day. All activities, food & drinks recorded in diaries.FastedNo moderate-heavy exercise1 week
NameEffects on test meal intake at approximately 4 h post-preloadEffects on test meal intake at approximately 8 h post-preloadEffects on test meal intake at approximately 12 h post-preloadEffects on test meal intake over following dayEffects on subjective ratingsIll effects/discomfortPleasantness
Treatment vs. placeboTreatment vs. placeboTreatment vs. placeboTreatment vs. placeboTreatment vs. placebo
  • *

    Estimated, based on 2 years prior to date of publication.

  • estimation of amount of Fabuless fats based on other formulations.

  • F, female; M, male; max, maximum; N/A, not applicable; P, placebo; prot., protein; carb., carbohydrate; T, treatment; VAS, Visual Analogue Scales; WS, within subjects.

Burns et al. (4), Study 1Energy [DOWNWARDS ARROW]Energy [DOWNWARDS ARROW]Hunger [DOWNWARDS ARROW]No effectsNo differences
Macronutrient [DOWNWARDS ARROW]Macronutrient [DOWNWARDS ARROW]Desire to eat [DOWNWARDS ARROW]
Weight [DOWNWARDS ARROW]Weight [DOWNWARDS ARROW]Preoccupation with thoughts of food [DOWNWARDS ARROW]
Burns et al. (4), Study 2Energy [DOWNWARDS ARROW]Energy [DOWNWARDS ARROW]No effectsNo effectsNo differences
Macronutrient [DOWNWARDS ARROW]Macronutrient [DOWNWARDS ARROW]
Weight [DOWNWARDS ARROW]Weight [DOWNWARDS ARROW]
Burns et al. (5)Energy [DOWNWARDS ARROW]Energy [DOWNWARDS ARROW]Energy [DOWNWARDS ARROW]Energy [DOWNWARDS ARROW]Hunger [DOWNWARDS ARROW]No effectsNo differences
Macronutrient [DOWNWARDS ARROW]Macronutrient [DOWNWARDS ARROW]Macronutrient [DOWNWARDS ARROW]Macronutrient [DOWNWARDS ARROW]Desire to eat [DOWNWARDS ARROW]
Weight [DOWNWARDS ARROW]Weight [DOWNWARDS ARROW]Weight [DOWNWARDS ARROW]Weight [DOWNWARDS ARROW]Preoccupation with thoughts of food [DOWNWARDS ARROW]
In lean and overweight.In lean, overweight and obese.In lean.In lean and obese.Fullness [UPWARDS ARROW]
Burns et al. (6)Energy [DOWNWARDS ARROW]Energy [DOWNWARDS ARROW] Energy [DOWNWARDS ARROW]No effectsNo effectsNo differences
Macronutrient [DOWNWARDS ARROW]Macronutrient [DOWNWARDS ARROW]Macronutrient [DOWNWARDS ARROW]
Weight [DOWNWARDS ARROW]Weight [DOWNWARDS ARROW]Weight [DOWNWARDS ARROW]
At all dosesAt all dosesAt all doses.
Study BFEnergy [DOWNWARDS ARROW]No effectsNo effectsNo effectsNo differences
Logan et al. (7)No differencesNo differencesNo differencesNo differences
Diepvens et al. (16)No differencesHunger [DOWNWARDS ARROW]No differences
Desire to eat [DOWNWARDS ARROW]
Return to baseline hunger – slower
In young lean group.
Study U1No effects
Smit et al. (17)No differencesEnergy [DOWNWARDS ARROW] Weight [DOWNWARDS ARROW]No effectsNo effectsNo differences
For unprocessed treatment
Study U3No differencesNo differencesNo differencesNo effects
Study U4No differencesNo differencesNo differencesNo effects
DSMNo differencesNo differencesNo differencesNo effects

Treatments were provided in a yoghurt, yoghurt drink, milk-based drink or soup vehicle, and provided different doses of Fabuless™ fats. Burns et al. (5) used 0.8 g Fabuless™ fats; Burns et al. (6) and study U3 used 2 g; study U1 used 2.5 g; study U3 used 3.2 g; Burns et al. (6) and Diepvens et al. (16) used 4 g and study BF is estimated to have used 4 g; Burns et al. (4, studies 1 and 2), Burns et al. (5), Logan et al. (7), Smit et al. (17), U4 and DSM used 5 g; and Burns et al. (6) used 6 g. In three studies, unprocessed Fabuless™ was used (6, 17, study BF), and in all others, excepting study U1, processed Fabuless™ was used, although type of processing varied between studies. Information on processing was unavailable for study U1. Preloads were given at 9:00 with the exception of those in study U3 which were given at 10:30, those in study U1 which were given at 12:00, and those in the study by Burns et al. (4) and study BF which were given at 13:00.

Appetite was assessed using buffet test meals, composed of 1 (16), 3 (17), 4 (studies U3, U4), 17 (6, DSM), 22 (study BF), 23 (5), 36 (4, studies 1 and 2) or 43 (7) foods, provided in either the dining area of a metabolic suite (4, studies 1 and 2; 5–7; study BF) or individual testing booths (17, studies U3, U4, DSM), 4 h after the preload, excepting in study U3 where the duration between preload and test meal was 3 h. Test meals lasted for an unlimited duration (4, studies 1 and 2, 5–7, study BF), 30 min maximum (17; studies U3; U4; DSM) or 20 min maximum (16). A second test meal was also provided in five studies (5; 17; studies U3; U4; DSM), composed of 3 (17), 4 (study U3), 5 (study U4), 14 (study DSM) and 36 (5) foods. Excepting the study by Diepvens et al. (16), all studies recorded subsequent intake for the rest of the day using either food diaries (4, studies 1 and 2, 5–7, study BF) or a snackbox plus food diaries (17; studies U3, U4, DSM). Three studies also recorded intake on the following day using food diaries (5–7). All studies measured appetite using subjective perceptions, and the majority of studies also measured ill effects/gastrointestinal complaints (5, 6, 17, studies BF, U1, U3, U4, DSM). Studies also used similar procedural controls with the exception of the Logan et al. (7) study, due to study design.

Studies for which data were available were combined, to provide an overall mean difference for Fabuless™ compared with control for test meal intake. Separate analyses were conducted for cumulative test meal intake at approximately 4 h, 8 h, 12 h and 36 h after preload, and studies with available data were included in each analysis. Due to the greater experimental control and the greater number of available studies, test meal intake at approximately 4 h post-preload was used as the primary outcome measure, and intake up to all other time points were considered as secondary outcome variables. Cumulative intake was analyzed as opposed to individual test meal intake at each time point to provide results relevant to everyday life. All studies with available data were included in each analysis. Studies with multiple treatments (6, 17, study U3) were included in each analysis, where each treatment was included separately. One study with multiple assessments (7) was included only once to abide by the assumptions of meta-analysis. In this case, data from the first day of testing were used, as this was comparable with all other studies. This resulted in the possible inclusion of 17 individual trials for analysis – Burns et al. (4) study 1; Burns et al. (4) study 2; Burns et al. (5); Burns et al. (6) 0.8 g dose; Burns et al. (6) 2 g dose; Burns et al. (6) 4 g dose; Burns et al. (6) 6 g dose; BF, unprocessed dose; BF, processed dose; Logan et al. (7) assessment day 1; Diepvens et al. (16); Smit et al. (17) unprocessed dose; Smit et al. (17) processed dose; U3, 2 g dose; U3, 3.2 g dose; U4; DSM.

Test meal intake at approximately 4 h post-preload

All studies available for analysis investigated test meal intake approximately 4 h post-preload. Initial combination of all studies using a random effects model showed a combined mean difference (Fabuless™ compared with control) of 0.53 MJ (95% confidence interval [CI] 0.20, 0.86), P < 0.01, although considerable heterogeneity between studies was also found (I2 = 97%, P < 0.01). Initial combination using a fixed effects model showed a combined mean difference (Fabuless™ compared with control) of 0.24 MJ (95% CI 0.14, 0.33), P < 0.01. The forest plot from the random effects model is given in Fig. 1. These results suggest a small appetite suppressant effect of Fabuless™, although caution must be exercised due to the considerable heterogeneity.

image

Figure 1. Forest plot showing combined effect of treatment vs. placebo for all studies investigating test meal intake at approximately 4 h post-preload. Studies arranged in order of year of completion. A combined effect of 0 represents no effect, a combined effect >0 represents an effect in favour of the treatment (lower test meal intake following treatment compared with placebo), a combined effect <0 represents a combined effect in favour of the placebo (lower test meal intake following placebo compared with treatment).

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To investigate this heterogeneity, meta-regression was conducted on data from all 17 individual studies from the random effects model, where weighted study mean differences were predicted by all variables of potential importance in determining energy intake that were found to differ between studies. These variables were: gender of participants (proportion who were female), age of participants (mean), body mass index (BMI) of participants (mean), dose of treatment, processed nature of treatment (unprocessed vs. processed), time of treatment (time of preload), composition of the test meal (number of foods), test setting, and year of study. Study mean data for gender, age and BMI were used initially to ensure inclusion of all data for all studies. Test setting included location of study (Ulster/Bristol/Maastricht), test meal setting (dining area of a metabolic suite/individual test booths/unknown) and time allowed for consumption of the test meal (unlimited/30 min maximum/20 min maximum.). All these variables co-varied exactly, and were included in the analyses either as one dichotomous variable or as three dummy variables (Test setting [Ulster], Test setting [Bristol], Test Setting [Maastricht]). Year of study was considered to be 2 years prior to the date of publication for all published studies unless known.

The results of the meta-regression on data investigating test meal intake approximately 4 h post-preload are given in Table 2. These results suggest that the differences between studies are, at least in part, a result of differences in year of study, treatment dose, and the sex, mean age and mean BMI of participants.

Table 2.  Coefficients for all variables in the meta-regression for test meal intake at approximate 4 h post-preload
VariableCoefficientSETP95% CI
  1. BMI, body mass index; CI, confidence interval; SE, standard error; T, t-value; P, P-value.

Sex of participants (% female)−0.0780.0312.500.05−0.155, −0.002
Age of participants0.4140.1662.490.050.007, 0.821
BMI of participants−0.8070.2772.910.03−1.485, −0.129
Dose of treatment0.2840.1012.800.030.356, 0.532
Processed nature of treatment (unprocessed = 1, processed = 2)−0.2140.3870.550.60−1.161, 0.724
Time of treatment0.1610.2030.790.46−0.335, 0.658
Number of foods in test meal−0.1050.0452.320.06−0.215, 0.006
Test setting (setting Bristol = 1, other = 2)0.1130.9340.120.91−2.173, 2.398
Test setting (setting Maastricht = 1, others = 2)−0.3480.8110.430.68−2.334, 1.637
Year of study−0.4340.1133.830.01−0.712, −0.157

To investigate possible effects of year of study, sensitivity analyses were conducted on all studies conducted before 2003, and all studies conducted after 2003. For all studies conducted before 2003 (n = 9), the results from a random effects model showed a combined mean difference (Fabuless™ compared with control) of 1.07 MJ (95% CI 0.58, 1.55), P < 0.01, although considerable heterogeneity between studies was found (I2 = 86%, P < 0.01). For all studies conducted after 2003 (n = 8), the results from a random effects model showed a combined mean difference (Fabuless™ compared with control) of −0.11 MJ (95% CI −0.22, 0.01), P = 0.08, with no heterogeneity between studies (I2 = 4%, P = 0.47). These results suggest an appetite suppressant effect of Fabuless™ vs. control in short-term studies conducted before 2003, although this result should be treated with caution due to the considerable heterogeneity, and show no effect in short-term studies conducted after 2003.

To investigate possible effects of dose of treatment, sensitivity analyses were conducted on all studies using less than 5 g Fabuless™, and all studies using 5 g Fabuless™ or more. For all studies using a dose of less than 5 g (n = 8), the results from a random effects model showed a combined mean difference (Fabuless™ compared with control) of 0.47 MJ (95% CI 0.02, 0.93), P = 0.04, although considerable heterogeneity between studies was found (I2 = 87%, P < 0.01). For all studies using a dose of 5 g or more (n = 9), the results from a random effects model showed a combined mean difference (Fabuless™ compared with control) of 0.58 MJ (95% CI 0.08, 1.08), P = 0.02, although again considerable heterogeneity between studies was found (I2 = 98%, P < 0.01). These results suggest an appetite suppressant effect of Fabuless™ vs. control using both doses of less than 5 g Fabuless™ and doses of 5 g Fabuless™ or more, although the results of both meta-analyses should be treated with caution due to high heterogeneity.

To investigate possible effects of participant sex, age and BMI, individual data were used as opposed to study mean data. Individual data were available for all studies excepting two (studies BF, 16), although where only one individual existed in any one sex, age or BMI category in any study, data from this individual also could not be used in this analysis. Using these data, no effects of sex (B = 0.14, 95% CI −0.48, 0.76, P = 0.65), age (B = −0.19, 95% CI −0.77, 0.39, P = 0.51), or BMI (B = −0.14, 95% CI −0.77, 0.50, P = 0.67) were found.

Subsequent intake up to approximately 8, 12 and 36 h post-preload (Cumulative Intake)

Similar analyses were also conducted for cumulative intake up to approximately 8, 12 and 36 h post-preload, although intake was not measured using test meals in all studies at these time points. Instead, in some studies and at some time points intake was measured using snack boxes (studies U3, U4, DSM), and in others or at other time points intake was measured using food diaries (4, studies 1 and 2, 5–7, study BF).

At approximately 8 h post-preload (measured in nine studies), initial combination using a random effects model showed a combined mean difference (Fabuless™ compared with control) of 0.64 MJ (95% CI −0.02, 1.29), P = 0.06, although considerable heterogeneity between studies was found (I2 = 93%, P < 0.01). Two meta-regressions (one investigating personal factors, one investigating procedural factors) suggested that none of the variables included in the models accounted for the heterogeneity between studies (largest B = −0.54, 95% CI −1.30, 0.21, P = 0.09).

At approximately 12 h post-preload (12 studies), initial combination using a random effects model showed a combined mean difference (Fabuless™ compared with control) of 2.37 MJ (95% CI 0.83, 3.91), P < 0.01, although considerable heterogeneity between studies was found (I2 = 97%, P < 0.01). Two meta-regressions (one investigating personal factors, one investigating procedural factors) suggested that the heterogeneity between studies was, at least in part, related to the processed nature of the treatment (unprocessed vs. processed) (B = −3.74, 95% CI −6.25, −1.24, P = 0.02) and Fabuless™ dose (B = 0.54, 95% CI 0.06, 1.03, P = 0.04).

Investigation of possible effects due to the processed nature of Fabuless™ revealed a combined mean difference of 5.21 MJ (95% CI 3.78, 6.64), P < 0.01 in studies using unprocessed Fabuless™ (n = 4) (I2 = 88%, P < 0.01), and no effect in studies using processed Fabuless™ (n = 6) (combined mean difference = 0.51 MJ [95% CI −0.50, 1.52], P = 0.32; I2 = 94%, P < 0.01). Investigation of effects due to dose of Fabuless™ suggested an appetite suppressant effect (combined mean difference = 2.74 (95% CI 0.32, 5.16), P = 0.03) in studies using a dose of less than 5 g (n = 5) (I2 = 98%, P < 0.01), and no effect in studies using 5 g or more (n = 5) (combined mean difference = 2.01 (95% CI −0.30, 4.31), P = 0.09; I2 = 98%, P < 0.01).

At approximately 36 h post-preload (six studies), initial combination of all studies using a random effects model showed a combined mean difference (Fabuless™ compared with control) of 5.69 MJ (95% CI 3.32, 8.06), P < 0.01, although considerable heterogeneity between studies was also found (I2 = 94%, P < 0.01). Meta-regression suggested that none of the variables included in the model accounted for the heterogeneity between studies (largest B = 0.90, 95% CI – 0.11, 1.90, P = 0.06).

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflicts of Interest Statement
  9. Acknowledgements
  10. References

Effect of Fabuless™ on test meal intake

Initial combination of all studies available at each time point showed an appetite suppressant (reduced food intake) effect of Fabuless™ compared with control. Specifically, Fabuless™ reduced cumulative energy intake at 4, 12 and 36 h post-preload, with a marginal effect at 8 h post-preload. However, caution must be exercised in respect of any conclusion about the effects of Fabuless™ on food intake due to considerable heterogeneity between studies. Heterogeneity refers to the variability or differences between study results (11,12). The considerable heterogeneity here suggests marked variability between studies, making the combined mean differences difficult to interpret and of limited predictive validity.

The random effects model investigating effects at approximately 4 h post-preload showed a combined mean reduction in calorie intake of ∼0.53 MJ (equalling ∼125 kcal) relative to control. Although the magnitude of this effect appears small, using data from the National NHANES survey, it was calculated that affecting energy balance by approximately 100 kcal day−1 could influence weight gain in most of the US population (18). Although caution must be exercised in respect of any conclusion about the effects of this vegetable oil emulsion on food intake due to considerable heterogeneity between studies, it is of interest that small differences in calorie intake may be relevant in a weight maintenance context.

Sources of heterogeneity

Meta-regression suggested that the heterogeneity between studies is, at least in part, due to differences in year of study (4 h post-preload); the processed vs. unprocessed nature of the treatment (12 h post-preload), and treatment dose (4 and 12 h post-preload).

Effects related to year of study were found where an appetite suppressant effect of Fabuless™ compared with control was apparent 4 h post-preload in studies conducted before 2003, but no significant food intake effect was found in studies after 2003. Heterogeneity, however, is very high for the earlier studies, although the later studies show good agreement. These differences in findings are most plausibly explained as an effect due to the manufacture, processing or preparation of Fabuless™ during the time period over which these studies were conducted. The Fabuless™ product is a manufactured food ingredient, which is processed further when added to food products. Fabuless™ can be incorporated into fermented milk products, such as yoghurt, using processing procedures common in the dairy industry, with certain precautions to ensure the integrity of the Fabuless™ emulsion structure. Over the years it has become clear that Fabuless™ should be dispersed in fine droplets throughout a vehicle product (Sein, 2010, DSM, personal communication), and is susceptible to breakdown when exposed to high shear forces at low temperatures and an acid environment. Other fats or emulsions and dehydration may also affect emulsion integrity. A high salt content, such as that found in soups can also destabilize the emulsion, especially if sterilized in liquid form to achieve a long shelf-life (Viberg, 2008, DSM, personal communication). In addition, Fabuless™ is made from natural products with possible seasonal variation. This is particularly true for the oat oil and its molecular composition, but whether these changes affect the behavior of the emulsion in the gastro-intestinal track is difficult to predict or study (Sein, 2010, DSM, personal communication). All these factors influencing the nature of Fabuless™ during the processing, however, have only gradually been elucidated over time and were not recorded in detail in each of the studies.

The suggestion that effects of year may be a result of differences in the manufacturing or processing of Fabuless™ is also supported by the effects found based on the processed nature of the treatment at 12 h post-preload, where effects were found using unprocessed Fabuless™, while no effects were found using processed Fabuless™. This finding strongly suggests that activities that occur as part of the processing of Fabuless™ have in some studies rendered the treatment inactive. It is important however to stress that the high levels of heterogeneity in these analyses and the presence of effects only at 12 h post-preload, suggest that these results should again be treated with considerable caution.

Effects of treatment dose on food intake are unclear. Sensitivity analyses on effects after 4 h did not confirm an effect of dose, but after 12 h indicate a greater appetite suppressant effect of Fabuless™ using doses of less than 5 g and no effect using higher doses. These findings suggest that low doses of Fabuless™ may suppress appetite more effectively than high doses, and this is supported by data from studies in which 2 g doses of Fabuless™ were found to reduce food intake (e.g. study BF). Meta-regression coefficients, however, suggest greater effects using higher doses, as was also observed in the dose–response study by Burns et al. (6). The discrepancy between the results of the sensitivity analyses and the meta-regressions indicates that effects of treatment dose are highly influenced by other variables included in the meta-regression models. Given the additional effects of year of study and the processed nature of the treatment, it is possible that the effects of treatment dose revealed in the sensitivity analyses are, likewise, actually due to differences between studies in the manufacturing or processing of Fabuless™. These effects highlight also the difficulties of conducting meta-analyses on limited and highly variable data.

No relationships were found between the appetite suppressant effects of Fabuless™ and the sex, age or BMI of participants in all studies, the timing of the preload, test setting or number of foods in the test meal. In other words, Fabuless™ had similar effects, or lack of effect, compared with control in both males and females, in individuals of different ages, in individuals of different BMIs, when provided at 9:00, 10:30 and 13:00, and when tested in different settings using different test meals. Effects of age were previously reported by Burns et al. (5) and Diepvens et al. (16) where greater effects were found in younger compared with older participants, but in both studies, age was confounded by BMI. Effects of BMI have previously been reported, where effects were found to be inversely related to weight group (5,16). This was explained as a result of lower satiating properties of fat in obese groups (19), but BMI groups in these studies were confounded by age. No other studies have reported different effects dependent on body weight. These findings have implications for the potential value of Fabuless™ in the real world, and suggest equal likelihood of effect (or lack of effect) in a variety of individuals and a variety of situations.

The absence of clear findings in some analyses and the heterogeneity or variability between studies found in all but one sensitivity analysis highlight the difficulties of conducting and interpreting meta-analyses where only limited and highly varied studies are available. The meta-analyses here are clearly limited in this respect. It is unfortunate that data from all studies using Fabuless™ were not available. The studies that were unavailable to us for reasons of confidentiality are also likely to have found no differences between treatment and control, resulting in a possible bias in the combined mean differences given here (13). There also remains the possibility that the present analyses have failed to identify a key factor affecting the outcome of these studies on the appetite suppressant effects of Fabuless™. Considering the discussion on processing activities, it is unfortunate that information on the exact manufacturing and processing activities for all studies is not available. Numerous other differences in methodology are also likely to exist between studies. It was not possible to investigate these factors due to a lack of available information.

In investigating effects on appetite, the meta-analyses here are also limited by their focus on test meal intake. Previous studies have found that Fabuless™ reduced ratings of hunger as well as test meal intake (e.g. 5), although not all studies have found effects on hunger. Such results are relevant to the understanding of the usefulness of Fabuless™ for weight management, because, by decreasing hunger Fabuless™ may allow reduced intake to be subjectively more acceptable (16). Hunger ratings were not analyzed here due to limited availability of appropriate data.

With regard to weight management, the present analyses are also limited by their consideration only of short-term laboratory-based studies. Laboratory studies are highly controlled but conducted in artificial settings, so their relevance to the real world and naturalistic eating behaviours is questionable (8,9). Short-term studies also focus on fixed time periods, whereas human dietary intake may vary on an hourly and daily basis, and compensation or counter-compensation following short-term studies is well known (8,9). Short-term studies should ideally be conducted in controlled environments using the controlled measurement of food intake for as long as practical, but the limitations of this approach, particularly in relation to ecological validity must be accepted. Furthermore, while short-term studies are valuable in terms of accuracy and control, the assessment of efficacy in relation to weight control clearly requires longer-term studies.

Conclusion

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflicts of Interest Statement
  9. Acknowledgements
  10. References

In conclusion, the combination of these short-term studies suggests a small appetite suppressant (reduced food intake) effect of Fabuless™ compared with control, although considerable heterogeneity or variability between studies was also found. This heterogeneity suggests the combined effects found are variable, difficult to interpret and difficult to predict. This heterogeneity was partly explained by differences between studies in the processed nature of the treatment, treatment dose and in particular year of study, but caution should again be exercised in relation to these conclusions due to the considerable heterogeneity also found in the sensitivity analyses. The only consistent finding was the absence of food intake effects found in studies conducted after 2003.

Conflicts of Interest Statement

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflicts of Interest Statement
  9. Acknowledgements
  10. References

This work was funded by DSM, the Netherlands, http://www.dsm.com. There are no other conflicts of interest.

Acknowledgements

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflicts of Interest Statement
  9. Acknowledgements
  10. References

Grateful thanks are extended to the authors and sponsors of unpublished studies for the provision of methodological details and data. This work was funded by DSM, the Netherlands, http://www.dsm.com. DSM identified all known studies, aided with the discussions on the aspects of methodology to be considered, and aided with discussions on potential mechanisms for effects. All contributions from DSM have been acknowledged in the text. Data abstraction and analysis were undertaken solely by the researchers.

References

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  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflicts of Interest Statement
  9. Acknowledgements
  10. References
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