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Can alginate-based preloads increase weight loss beyond calorie restriction? A pilot study in obese individuals
Appetite 57 (2011) 601–604
Contents lists available at ScienceDirect
Appetite journal homepage: www.elsevier.com/locate/appet
Short communication
Can alginate-based preloads increase weight loss beyond calorie restriction? A pilot study in obese individuals§ M. Georg Jensen *, M. Kristensen, A. Astrup Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Rolighedsvej 30, DK-1958 Frederiksberg C, Denmark
A R T I C L E I N F O
A B S T R A C T
Article history: Received 14 February 2011 Received in revised form 23 June 2011 Accepted 5 July 2011 Available online 14 July 2011
This randomized, controlled, 2-week intervention study in 24 obese subjects tested the effect on body weight loss and gastrointestinal tolerance of consuming low viscous alginate fibre-based preloads of 3% concentration (500 ml volume) three times a day as an adjuvant to a calorie-restricted diet. The pilot study showed that intake of the alginate preloads was moderately acceptable to the majority of subjects but did not produce additional body weight loss beyond calorie restriction ( 1.42 0.38 kg) (n = 12) compared to control group ( 1.56 0.21 kg) (n = 8). These results do not support that alginate supplementation enhance the weight loss effects of a hypo-caloric diet, but a sufficiently powered longterm study is needed to explore whether alginate could be an aid for improving weight loss during caloricrestriction. ß 2011 Elsevier Ltd. All rights reserved.
Keywords: Dietary fibre Alginate Liquid preload Weight loss Gastrointestinal tolerance Palatability
Introduction It has been reported that dietary fibres could be a useful tool in addressing obesity management due to its effects on appetite sensation, the major mechanism involved in control of energy intake (Howarth, Saltzman, & Roberts, 2001; Slavin, 2005). Alginates are dietary fibres extracted from brown seaweed, which show viscous physiological properties and form gel lumps when exposed to an acidic environment as that found in the human stomach. This gel formation is suggested to delay gastric emptying rate, stimulate gastric stretch receptors and slow nutrient absorption in the small intestine (Hoad et al., 2004). There have only been limited acute or short-term studies (Dettmar, Strugala, & Craig Richardson, 2011) of the effect of alginate supplementation on appetite control and food intake, and these studies have had inconclusive results (Mattes, 2007; Odunsi et al., 2009). However, for hydrated alginates in liquid formulations there exists some evidence that supplementation reduce energy intake under free-living conditions. In a recent study,
§ MGJ, MK and AA planned the study, and MGJ wrote the protocol and conducted the study. MGJ analysed the data with MK and AA. MGJ wrote the manuscript and the remaining authors all reviewed the manuscript. Author MGJ is supported by a research grant from S-Biotek Holding ApS and AA is in the advisory board at SBiotek Holding ApS. This work is also supported by grants from FOOD Research School/LIFE, University of Copenhagen, Denmark. None of the authors had any conflict of interest to declare. The authors express their gratitude to the dieticians M. Juhl and P. Ha˚konson for dietary counselling and to all subjects for participating in the pilot study. * Corresponding author. E-mail address: [email protected] (M. Georg Jensen).
0195-6663/$ – see front matter ß 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.appet.2011.07.004
1 week of daily ingestion of a strong-gelling alginate supplement based on 1.5 g fibre in the form of a 100 ml preload beverage resulted in a significant decrease of energy intake ( 7%) compared to a control group (Paxman, Richardson, Dettmar, & Corfe, 2008). A similar reduction in daily energy intake ( 10%) was seen in overweight women with low rigid restraint scores who consumed a beverage containing 1 g or 2.8 g doses of alginate-pectin twice daily for 1 week (Pelkman, Navia, Miller, & Pohle, 2007). We have previously investigated a liquid alginate-based preload specifically designed to modify appetite sensation by forming a viscous gel in the stomach, which we found increased satiety and decreased hunger in acute setting (Jensen, Kristensen, Belza, Knudsen, & Astrup, 2011). The hunger-reducing effects of alginate suggest that this fibre may be useful during energy restriction for short-term weight loss and to our knowledge nobody has yet investigated the effect of supplementation solely based on alginate on changes in body weight. The primary aim of this study was therefore to investigate if 2 weeks supplementation of 15 g of strong gelling alginate dissolved in 500 ml water three times a day in combination with a hypocaloric diet could enhance weight loss and decrease waist circumference in obese subjects compared to a control preload. In addition, gastrointestinal adverse events and compliance to preload consumption were included as secondary objectives. Methods The pilot study was designed as a double-blind parallel intervention of 2 weeks duration during which all subjects
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M. Georg Jensen et al. / Appetite 57 (2011) 601–604
consumed a caloric-restricted diet. Subjects were randomised into two groups; one group consumed an alginate-based preload beverage and the other group consumed a control preload beverage. To be included in the study, subjects had to be healthy obese individuals with a BMI of 30–40 kg/m2 and aged between 20 and 45. Exclusion criteria were: smoking, known chronic illnesses (e.g. diabetes or CVD), hypertension (>160/100 mmHg), elevated total cholesterol (>6.5 mmol/l), high level of physical activity (>10 h/ week), use of dietary supplements, food intolerances of relevance to the study, and regular use of prescription medication (except oral contraceptives). All participants attended a screening visit before enrolment where their eligibility was assessed and they gave their written consent after having received verbal and written information about the study. The Municipal Ethical Committee of Copenhagen and Frederiksberg (H-C-2008-088) approved the study and it was registered at ClinicalTrials.gov (NCT 01101633). A total of 24 subjects were found eligible for enrolment in the study. In order to achieve experience with the effect of alginate supplementation on weight loss, we used an unbalanced design with a randomisation ratio of 2:1, allowing 16 subjects to be randomised to the alginate group and 8 to the control group. Preload beverages Both types of preloads were based on 500 ml water, artificial sweetener (0.05 g aspartame) and fruit flavour (1.2 g), aiming at a similarity in flavour and appearance. Preload beverages were prepared by mixing powder and water while stirring, and then bottled (by Fussgaard A/S, Denmark) before study start. Preload beverages were coded, labelled and stored in our metabolic kitchen at 5 8C. All subjects were instructed to consume one preload beverage 30 min before each main meal, i.e. three times daily. The alginate-based preload contained 15 g of sodium alginate (=9.5 crude dietary fibre), equivalent to a 3% alginate concentration (AlgogelTM DPG JO, Cargill A/S). The manufacture described AlgogelTM DPG JO to have a particle size of 90% less than 250 mm and a molecular weight of approximately 50.000 kDa, which make this a low viscosity alginate. With nuclear magnetic resonance spectroscopy we analyzed the alginate to have a mannuronic:guluronic acid ratio of 0.8, which imply high gel strength due a high guluronic acid content. The average viscosity was approximately 1.0 mPa s for the control and 40.0 mPa s for the alginate beverage measured by a Bohlin C-VOR rheometer (Malvern Instruments Ltd., UK) at neutral pH value with a constant temperature. Gelling properties of the alginate preloads at acidic conditions, similar to stomach pH, were studied as well. Oscillatory shear rheology performed on a Bohlin C-VOR rheometer (Malvern Instruments Ltd., UK) was used to quantify mechanical properties of acid alginate gels, and an average elastic modulus [Pa] was calculated and denoted as gel strength [Pa]. The gel strength for the alginate-based beverage was measured to be 1141 12 [Pa], and no gel was formed from the control beverage. The calorie-restricted diet The weight loss program was based on an educational system, consisting of five colour-coded iso-caloric interchangeable units of 250 kJ representing different nutrients (protein-rich, complex carbohydrate-rich, simple carbohydrate-rich, fat-rich and alcohol). With the aim of inducing weight loss (0.5 kg per week), all subjects were instructed to adhere to a low-fat diet (about 30% of energy from fat, 20% from protein, and 50% from carbohydrates) of at least five units ( 1250 kJ/d) less than estimated energy requirements assessed on sex, weight, height and physical activity level (Schofield, 1985). Subjects were instructed to keep a
complete food diary and met individually with a skilled dietician three times during the intervention. Anthropometric measures All measurements were performed at baseline, and at weeks 1 and 2 at the Department of Human Nutrition, University of Copenhagen in the morning after subjects had fasted for 10 h. Body weight was measured to the nearest 0.1 kg using an electronic scale while the subjects were wearing only underwear and no shoes. Height was measured to the nearest 0.5 cm by using a wall-mounted stadiometer while the subjects were wearing no shoes. Waist circumference was measured to the nearest 0.5 cm at the narrowest point between the iliac crest and the lowest rib. Gastrointestinal comfort registration A questionnaire was used to evaluate adverse events in the gastrointestinal tract related to the consumption of the preload beverage. Subjects were asked to note, at the end of each day in the intervention period, their overall well-being and frequency of episodes of nausea, diarrhoea, rumbling stomach, reflux, bloatedness, flatulence, constipation and heartburn after consumption of the preloads. The questionnaire included a scale of severity of symptoms, which was set from 1 (indicating no discomfort) to 5 (indicating very strong discomfort). In addition, all subjects kept a defecation diary, marking each time they defecated and marking either ‘‘0 = loose’’ or ‘‘1 = firm’’ for the texture of the faeces. Compliance and palatability measurements To verify compliance, participants were required to note the answer to the question: ‘‘Did you drink the test beverage today?’’ with the choice of answers ‘‘No I did not drink it’’ = 0, ‘‘Some of it’’ = 1 or ‘‘Yes all of it’’ = 2, prior to breakfast, lunch and dinner every day during the 2-week intervention period. The subjects were asked to rate the palatability of the preload beverage at baseline, and at weeks 1 and 2, using a questionnaire from ‘‘1 = really good taste’’ to ‘‘5 = really bad taste’’. Statistical methods All statistical analyses were performed in SAS1System for Windows (release 9.1, SAS institute inc., Cary, NC). All data are presented as means SE unless otherwise indicated, and the statistical significance level is defined as P < 0.05. Data were tested for homogeneity of variance using the Shapiro–Wilk W-test and the normal distribution was inspected using normal probability plots. A repeated measures ANCOVA analysis (performed in PROC MIXED) was used to examine the effect of treatment (alginate vs. control) and time (0, 1 and 2 weeks), and their effect on body weight, waist circumference and taste preferences with sex and baseline body weight as covariates. Post hoc pair-wise comparisons were made using Tukey Kramer’s adjustment when the main analysis indicated a significant treatment effect. Additionally post hoc analysis with poor compliers removed defined as subjects consuming less than 85% of the preload beverages were conducted. The Wilcoxon signed rank sum test was used to examine differences between treatment groups in relation to compliance, frequency of self-reported adverse events and defecation (performed in PROC NPAR1WAY). Results A total of 20 subjects completed the pilot study, 12 in the alginate group and 8 in the control group. Four participants from the alginate group dropped out during the first week; three due to dislike of the
M. Georg Jensen et al. / Appetite 57 (2011) 601–604 Table 1 Compliance (%) for preload consumption over the 2-week intervention period (n = 20). No, I did not consume the preload beverage
I only drank some of the beverage
Breakfast preload Alginate 18.5%*** 4.7% Control 3.6% 0.0% Lunch preload Alginate 10.7%** 2.4% Control 0.0% 0.0% Dinner preload Alginate 5.3%* 4.2% Control 0.9% 0.0% Overall compliance (total of all three preloads) Alginate 11.5% 3.8% Control 1.5% 0.0%
Yes, I consumed the hole preload beverage 76.8% 96.4% 86.9% 100.0% 90.5% 99.1% 84.7%*** 98.5%
% calculation are within the groups (=rows). P-value for difference between groups: *P = 0.01, **P = 0.002, ***P = 0.0001.
preload beverage and one because of gastrointestinal discomfort. Baseline body weight (103.4 14.0 kg), BMI (33.8 3.3 kg/m2), waist circumference (106.6 9.0 cm) and age (35.7 7.5 years) did not differ between the two groups (P > 0.1). Compliance and palatability As shown in Table 1, we found an effect of time (P = 0.04) and treatment (P = 0.0001) on self-reported overall compliance, with 85% of subjects in the alginate group answering yes to the question ‘‘Did you drink the preload beverage today?’’ at the end of the 2week intervention compared to 98% in the control group. The lower compliance in the alginate group seems to be a result of difficulties with consumption of the breakfast preload (see Table 1). When analysing the individual compliance of the 20 subjects who completed the intervention, three subjects in the alginate group had a poor compliance with less than 85% of preload consumed. All subjects in the control group had a compliance >95%. The ratings on preload palatability were collected three times over the 2-week intervention period, with no effect of time observed (P = 0.2). However, there was a treatment effect on overall palatability with a slightly higher (and thereby worse) taste rating of the alginate-based preload (3.4 0.1 points) compared to control (3.0 0.1 points) (P = 0.05). Difference in palatability between groups did not change after exclusion of poor compliers. Anthropometry After 2 weeks, we observed a decrease in body weight in both groups (P = 0.02); however, this weight loss did not differ between groups ( 1.42 0.38 kg vs. 1.56 0.21 kg in the alginate and control group, respectively) (P = 0.4). When analyzing weight loss data after poor compliers (<85%) had been removed, the alginate group now exhibit a greater numerical decrease of 1.95 0.33 kg in body weight compared to 1.56 0.21 kg in the control group, however this difference did not reach significance (P = 0.33). Additionally, waist circumference decreased in both groups (P = 0.001); but again, there was no difference between group means ( 1.82 0.9 cm vs. 2.56 1.0 cm for alginate and control group, respectively) (P = 0.2). Although non-significant, removal of poor compliers resulted in a numerical larger difference between waist circumference for the control group 2.56 0.4 cm compared to 1.06 1.0 cm in the alginate group (P = 0.19). Gastrointestinal adverse events The self-reported answers on overall well-being after preload consumption during the 2 weeks revealed that 41% in the alginate
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group versus 58% in the control group felt ‘very well’ (P = 0.005). In addition, more subjects from the alginate group (17%) felt ‘moderately well’ after preload consumption compared to 4% in the control group (P = 0.001). When analysing well-being without the three poor compliers from the alginate group the difference in feeling ‘very well’ was no longer significant between groups (51% vs. 58% for alginate and control, respectively) (P = 0.25). No change in the results on feeling ‘moderately well’ was observed after removing poor compliers. We found an effect of treatment on self-reported adverse events, with higher frequency (13%) of a weak degree of diarrhoea after consumption of the alginate-based preload compared to control (1%) (P = 0.0001). The control group reported a higher frequency of a weak degree of constipation (13% vs. 2%, P = 0.007) and a moderate degree of flatulence (17% vs. 5%, P = 0.007) compared to the alginate group. No difference between groups was found in any of the other specific adverse events. No change in the results on self-reported adverse events was observed after removing poor compliers. During the intervention, we found a time (P = 0.005) and treatment effect (P = 0.04) on faeces texture, as 47% in the alginate group answered that their faeces had a more ‘loose’ texture compared to 16% in the control group. Frequency of defecation did not differ between groups (P = 0.3). No change in the results on faeces texture was observed after removing poor compliers. Discussion Our hypothesis was that alginate fibre as an adjuvant to a modest energy-restricted diet could improve body weight loss in obese subjects. However, no difference in weight loss or waist circumference was observed between groups during the 2-week study period, while compliance to preload consumption as well as palatability ratings differed between groups. We have previously shown that consumption of this alginate preload affected satiety, hunger feelings and energy intake in an acute meal test study (Jensen et al., 2011), although the observed reduction in ad libitum energy intake of the alginate preload in the acute study was modest ( 5%). However, if this effect could be extrapolated to a consistent decrease in energy intake by administration of three preloads daily, it is possible that such an energy deficit could affect the energy balance. We therefore anticipated that, if these suppressive effects on appetite occurred consistently during regular consumption, a larger decrease in body weight, beyond the modest energy-restricted diet, would be observed. After the post hoc analysis with poor compliers removed we found a numerical larger weight loss compared to the control group. However this was still non-significant, which could indicate that even when complying with the alginate treatment, no additional effect on weight loss could be produced. The lower compliance seen in the alginate preload group is probably related to the lower palatability of the preload. When we developed the preloads it was our aim to match the sensory properties; unfortunately, we were not successful in doing this, which is a limitation of the study. We did not collect information on sensory parameters such as mouth feel and texture of the preload; however we speculate that the lower compliance to consume the alginate beverage was perhaps due to the difference in preload viscosity. Even though the alginate beverage was based on a low-viscosity alginate, it still had a less attractive or perhaps ‘‘slimy’’ mouth feel compared to the control beverage. A decreased palatability of alginate formulations has also been reported by others (Hoad et al., 2004; Mattes, 2007), and it represents a recurrent challenge when adding viscous fibres to beverages. A possible reason for the lack of effect on body weight observed is the relatively small number of subjects enrolled and the short
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duration of the study, indicating that the study was underpowered to detect differences in body weight. In another shortterm study with 28 subjects that investigated the effect of a semisolid meal with or without added guar gum, a similar body weight loss over 2 weeks was found (Kovacs et al., 2001). This stresses that when investigating fibre supplementation and changes in body weight, longer duration of the intervention is required in order to detect a significant difference. However, it could be that alginate supplementation through suppression of hunger exhibits its effect as a better adherence to at hypo-caloric diet for a longer period of time. Therefore, it would be relevant to investigate whether consumption of alginate could act as an aid during lifestyle modifications such as changing eating behaviour with a view to losing weight. In conjunction to this, most studies investigating the effect of dietary fibre on appetite regulation, suggest that the type of fibre, amount and vehicle of administration are important (Kristensen & Jensen, 2011). A strong-gelling alginate with a high guluronic acid content added to a meal-replacement showed better hunger-reducing effect compared to weak-gelling alginates primarily based on mannuronic acid (Hoad et al., 2004). Additionally, it has been shown that adding alginate to liquid preloads had a greater effect on appetite control than adding alginate to a solid preload (Mattes, 2007; Paxman et al., 2008; Pelkman et al., 2007). Even though the preload beverages in our study were based on the highest amount of alginate administered to this date, we still relied on gastric acid secretion for gel formation. There are two approaches to alginate gel formation: (1) through acidification and (2) through divalent ion binding. When pH of the alginate solution is lowered beyond the pKa of the guluronic acid (3.65) and mannuronic acid (3.38), gel formation occurs due to protonation of the carboxyl groups by addition of inorganic acid. Addition of a divalent ion such as Ca2+ to the alginate solution results in a gel formation due to efficient ionbinding ability of alginate (Draget et al., 2000). If our preload formulation had been fortified with Ca2+, we would likely have gel formation in the stomach independent of pH. This could point to that addition of multivalent cations is highly needed for sufficient gel formation when developing alginate formulations for dietary supplementation. Monitoring of overall well-being during the 2-week intervention period showed that this specific alginate was moderately acceptable to the majority of subjects. This observation is in line with earlier acute studies on alginate consumption assessing gastrointestinal comfort (Mattes, 2007; Pelkman et al., 2007; Williams et al., 2004; Wolf et al., 2002). It has been suggested that alginate fibres are more slowly fermented than other viscous fibres (Brownlee et al., 2005), which might make alginate a better tolerated fibre source than rapidly fermented fibres that are often associated with discomfort in the gastrointestinal region. Nevertheless, as no significant difference in gastrointestinal adverse event between groups was found after post hoc analysis after removal of poor compliers, this could indicate that some subjects did not adhere to the alginate supplementation because it reduced their feelings of well-being or that tolerability differs between individuals, which perhaps depend on their habitual dietary fibre intake. One subject dropped out due to diarrhoea, which also was
the adverse event reported most frequently a weak degree of discomfort after alginate consumption compared to control and a higher percentage reported loose stool in the alginate group compared to control. However the term ‘loose stool’ was not defined as diarrhoea in the guiding to the subjects, which possibly could reflect that the subjects merely experienced less constipation or a softer defecation. Based on these findings a continuous monitoring of gastrointestinal discomfort is advisable in future studies. In conclusion, the alginate-based preload beverage did not produce additional weight loss in obese subjects beyond that resulting from the calorie-restricted diet. However, this is possibly due to limitations of study design and that the alginate formulation was reliant only on gastric acid for gel formation followed consumption. Our findings further indicated that alginate supplementation for 2 weeks was moderately acceptable to the majority of subjects, but a few subjects did not tolerate the supplementation leading to a lower compliance of preload consumption. Whether long-term alginate supplementation could be a potential aid for improving adherence to caloric-restricted diet for weight loss still requires further research. References Brownlee, I. A., Allen, A., Pearson, J. P., Dettmar, P. W., Havler, M. E., Atherton, M. R., et al. (2005). Alginate as a source of dietary fiber. Critical Reviews in Food Science and Nutrition, 45(6), 497–510. Dettmar, P. W., Strugala, V., & Craig Richardson, J. (2011). The key role alginates play in health. Food Hydrocolloids, 25(2), 263–266. Draget, K. I., Strand, B., Hartmann, M., Valla, S., Smidsrod, O., & Skjak-Braek, G. (2000). Ionic and acid gel formation of epimerised alginates; the effect of AlgE4. International Journal of Biological Macromolecules, 27(2), 117–122. Hoad, C. L., Rayment, P., Spiller, R. C., Marciani, L., Alonso, B. C., Traynor, C., et al. (2004). In vivo imaging of intragastric gelation and its effect on satiety in humans. Journal of Nutrition, 134(9), 2293–2300. Howarth, N. C., Saltzman, E., & Roberts, S. B. (2001). Dietary fiber and weight regulation. Nutrition Reviews, 59(5), 129–139. Jensen, M. G., Kristensen, M., Belza, A., Knudsen, J. C., & Astrup, A. (2011). Acute effect of alginate-based preload on satiety feelings, energy intake and gastric emptying rate in healthy subjects. Obesity, doi:10.1038/oby.2011.232 [Epub ahead of print]. Kovacs, E. M., Westerterp-Plantenga, M. S., Saris, W. H., Goossens, I., Geurten, P., & Brouns, F. (2001). The effect of addition of modified guar gum to a low-energy semisolid meal on appetite and body weight loss. International Journal of Obesity Related Metabolic Disorders, 25(3), 307–315. Kristensen, M., & Jensen, M. G. (2011). Dietary fibres in the regulation of appetite and food intake. Importance of viscosity. Appetite, 56(1), 65–70. Mattes, R. D. (2007). Effects of a combination fiber system on appetite and energy intake in overweight humans. Physiology & Behavior, 90(5), 705–711. Odunsi, S. T., Vazquez-Roque, M. I., Camilleri, M., Papathanasopoulos, A., Clark, M. M., Wodrich, L., et al. (2009). Effect of alginate on satiation, appetite, gastric function, and selected gut satiety hormones in overweight and obesity. Obesity Silver.Spring: . Paxman, J. R., Richardson, J. C., Dettmar, P. W., & Corfe, B. M. (2008). Daily ingestion of alginate reduces energy intake in free-living subjects. Appetite, 51(3), 713–719. Pelkman, C. L., Navia, J. L., Miller, A. E., & Pohle, R. J. (2007). Novel calcium-gelled, alginate-pectin beverage reduced energy intake in nondieting overweight and obese women: interactions with dietary restraint status. American Journal of Clinical Nutrition, 86(6), 1595–1602. Schofield, W. N. (1985). Predicting basal metabolic rate, new standards and review of previous work. Human Nutrition-Clinical Nutrition, 39(Suppl. 1), 5–41. Slavin, J. L. (2005). Dietary fiber and body weight. Nutrition, 21(3), 411–418. Williams, J. A., Lai, C. S., Corwin, H., Ma, Y., Maki, K. C., Garleb, K. A., et al. (2004). Inclusion of guar gum and alginate into a crispy bar improves postprandial glycemia in humans. Journal of Nutrition, 134(4), 886–889. Wolf, B. W., Lai, C. S., Kipnes, M. S., Ataya, D. G., Wheeler, K. B., Zinker, B. A., et al. (2002). Glycemic and insulinemic responses of nondiabetic healthy adult subjects to an experimental acid-induced viscosity complex incorporated into a glucose beverage. Nutrition, 18(7–8), 621–626.
Contents lists available at ScienceDirect
Appetite journal homepage: www.elsevier.com/locate/appet
Short communication
Can alginate-based preloads increase weight loss beyond calorie restriction? A pilot study in obese individuals§ M. Georg Jensen *, M. Kristensen, A. Astrup Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Rolighedsvej 30, DK-1958 Frederiksberg C, Denmark
A R T I C L E I N F O
A B S T R A C T
Article history: Received 14 February 2011 Received in revised form 23 June 2011 Accepted 5 July 2011 Available online 14 July 2011
This randomized, controlled, 2-week intervention study in 24 obese subjects tested the effect on body weight loss and gastrointestinal tolerance of consuming low viscous alginate fibre-based preloads of 3% concentration (500 ml volume) three times a day as an adjuvant to a calorie-restricted diet. The pilot study showed that intake of the alginate preloads was moderately acceptable to the majority of subjects but did not produce additional body weight loss beyond calorie restriction ( 1.42 0.38 kg) (n = 12) compared to control group ( 1.56 0.21 kg) (n = 8). These results do not support that alginate supplementation enhance the weight loss effects of a hypo-caloric diet, but a sufficiently powered longterm study is needed to explore whether alginate could be an aid for improving weight loss during caloricrestriction. ß 2011 Elsevier Ltd. All rights reserved.
Keywords: Dietary fibre Alginate Liquid preload Weight loss Gastrointestinal tolerance Palatability
Introduction It has been reported that dietary fibres could be a useful tool in addressing obesity management due to its effects on appetite sensation, the major mechanism involved in control of energy intake (Howarth, Saltzman, & Roberts, 2001; Slavin, 2005). Alginates are dietary fibres extracted from brown seaweed, which show viscous physiological properties and form gel lumps when exposed to an acidic environment as that found in the human stomach. This gel formation is suggested to delay gastric emptying rate, stimulate gastric stretch receptors and slow nutrient absorption in the small intestine (Hoad et al., 2004). There have only been limited acute or short-term studies (Dettmar, Strugala, & Craig Richardson, 2011) of the effect of alginate supplementation on appetite control and food intake, and these studies have had inconclusive results (Mattes, 2007; Odunsi et al., 2009). However, for hydrated alginates in liquid formulations there exists some evidence that supplementation reduce energy intake under free-living conditions. In a recent study,
§ MGJ, MK and AA planned the study, and MGJ wrote the protocol and conducted the study. MGJ analysed the data with MK and AA. MGJ wrote the manuscript and the remaining authors all reviewed the manuscript. Author MGJ is supported by a research grant from S-Biotek Holding ApS and AA is in the advisory board at SBiotek Holding ApS. This work is also supported by grants from FOOD Research School/LIFE, University of Copenhagen, Denmark. None of the authors had any conflict of interest to declare. The authors express their gratitude to the dieticians M. Juhl and P. Ha˚konson for dietary counselling and to all subjects for participating in the pilot study. * Corresponding author. E-mail address: [email protected] (M. Georg Jensen).
0195-6663/$ – see front matter ß 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.appet.2011.07.004
1 week of daily ingestion of a strong-gelling alginate supplement based on 1.5 g fibre in the form of a 100 ml preload beverage resulted in a significant decrease of energy intake ( 7%) compared to a control group (Paxman, Richardson, Dettmar, & Corfe, 2008). A similar reduction in daily energy intake ( 10%) was seen in overweight women with low rigid restraint scores who consumed a beverage containing 1 g or 2.8 g doses of alginate-pectin twice daily for 1 week (Pelkman, Navia, Miller, & Pohle, 2007). We have previously investigated a liquid alginate-based preload specifically designed to modify appetite sensation by forming a viscous gel in the stomach, which we found increased satiety and decreased hunger in acute setting (Jensen, Kristensen, Belza, Knudsen, & Astrup, 2011). The hunger-reducing effects of alginate suggest that this fibre may be useful during energy restriction for short-term weight loss and to our knowledge nobody has yet investigated the effect of supplementation solely based on alginate on changes in body weight. The primary aim of this study was therefore to investigate if 2 weeks supplementation of 15 g of strong gelling alginate dissolved in 500 ml water three times a day in combination with a hypocaloric diet could enhance weight loss and decrease waist circumference in obese subjects compared to a control preload. In addition, gastrointestinal adverse events and compliance to preload consumption were included as secondary objectives. Methods The pilot study was designed as a double-blind parallel intervention of 2 weeks duration during which all subjects
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consumed a caloric-restricted diet. Subjects were randomised into two groups; one group consumed an alginate-based preload beverage and the other group consumed a control preload beverage. To be included in the study, subjects had to be healthy obese individuals with a BMI of 30–40 kg/m2 and aged between 20 and 45. Exclusion criteria were: smoking, known chronic illnesses (e.g. diabetes or CVD), hypertension (>160/100 mmHg), elevated total cholesterol (>6.5 mmol/l), high level of physical activity (>10 h/ week), use of dietary supplements, food intolerances of relevance to the study, and regular use of prescription medication (except oral contraceptives). All participants attended a screening visit before enrolment where their eligibility was assessed and they gave their written consent after having received verbal and written information about the study. The Municipal Ethical Committee of Copenhagen and Frederiksberg (H-C-2008-088) approved the study and it was registered at ClinicalTrials.gov (NCT 01101633). A total of 24 subjects were found eligible for enrolment in the study. In order to achieve experience with the effect of alginate supplementation on weight loss, we used an unbalanced design with a randomisation ratio of 2:1, allowing 16 subjects to be randomised to the alginate group and 8 to the control group. Preload beverages Both types of preloads were based on 500 ml water, artificial sweetener (0.05 g aspartame) and fruit flavour (1.2 g), aiming at a similarity in flavour and appearance. Preload beverages were prepared by mixing powder and water while stirring, and then bottled (by Fussgaard A/S, Denmark) before study start. Preload beverages were coded, labelled and stored in our metabolic kitchen at 5 8C. All subjects were instructed to consume one preload beverage 30 min before each main meal, i.e. three times daily. The alginate-based preload contained 15 g of sodium alginate (=9.5 crude dietary fibre), equivalent to a 3% alginate concentration (AlgogelTM DPG JO, Cargill A/S). The manufacture described AlgogelTM DPG JO to have a particle size of 90% less than 250 mm and a molecular weight of approximately 50.000 kDa, which make this a low viscosity alginate. With nuclear magnetic resonance spectroscopy we analyzed the alginate to have a mannuronic:guluronic acid ratio of 0.8, which imply high gel strength due a high guluronic acid content. The average viscosity was approximately 1.0 mPa s for the control and 40.0 mPa s for the alginate beverage measured by a Bohlin C-VOR rheometer (Malvern Instruments Ltd., UK) at neutral pH value with a constant temperature. Gelling properties of the alginate preloads at acidic conditions, similar to stomach pH, were studied as well. Oscillatory shear rheology performed on a Bohlin C-VOR rheometer (Malvern Instruments Ltd., UK) was used to quantify mechanical properties of acid alginate gels, and an average elastic modulus [Pa] was calculated and denoted as gel strength [Pa]. The gel strength for the alginate-based beverage was measured to be 1141 12 [Pa], and no gel was formed from the control beverage. The calorie-restricted diet The weight loss program was based on an educational system, consisting of five colour-coded iso-caloric interchangeable units of 250 kJ representing different nutrients (protein-rich, complex carbohydrate-rich, simple carbohydrate-rich, fat-rich and alcohol). With the aim of inducing weight loss (0.5 kg per week), all subjects were instructed to adhere to a low-fat diet (about 30% of energy from fat, 20% from protein, and 50% from carbohydrates) of at least five units ( 1250 kJ/d) less than estimated energy requirements assessed on sex, weight, height and physical activity level (Schofield, 1985). Subjects were instructed to keep a
complete food diary and met individually with a skilled dietician three times during the intervention. Anthropometric measures All measurements were performed at baseline, and at weeks 1 and 2 at the Department of Human Nutrition, University of Copenhagen in the morning after subjects had fasted for 10 h. Body weight was measured to the nearest 0.1 kg using an electronic scale while the subjects were wearing only underwear and no shoes. Height was measured to the nearest 0.5 cm by using a wall-mounted stadiometer while the subjects were wearing no shoes. Waist circumference was measured to the nearest 0.5 cm at the narrowest point between the iliac crest and the lowest rib. Gastrointestinal comfort registration A questionnaire was used to evaluate adverse events in the gastrointestinal tract related to the consumption of the preload beverage. Subjects were asked to note, at the end of each day in the intervention period, their overall well-being and frequency of episodes of nausea, diarrhoea, rumbling stomach, reflux, bloatedness, flatulence, constipation and heartburn after consumption of the preloads. The questionnaire included a scale of severity of symptoms, which was set from 1 (indicating no discomfort) to 5 (indicating very strong discomfort). In addition, all subjects kept a defecation diary, marking each time they defecated and marking either ‘‘0 = loose’’ or ‘‘1 = firm’’ for the texture of the faeces. Compliance and palatability measurements To verify compliance, participants were required to note the answer to the question: ‘‘Did you drink the test beverage today?’’ with the choice of answers ‘‘No I did not drink it’’ = 0, ‘‘Some of it’’ = 1 or ‘‘Yes all of it’’ = 2, prior to breakfast, lunch and dinner every day during the 2-week intervention period. The subjects were asked to rate the palatability of the preload beverage at baseline, and at weeks 1 and 2, using a questionnaire from ‘‘1 = really good taste’’ to ‘‘5 = really bad taste’’. Statistical methods All statistical analyses were performed in SAS1System for Windows (release 9.1, SAS institute inc., Cary, NC). All data are presented as means SE unless otherwise indicated, and the statistical significance level is defined as P < 0.05. Data were tested for homogeneity of variance using the Shapiro–Wilk W-test and the normal distribution was inspected using normal probability plots. A repeated measures ANCOVA analysis (performed in PROC MIXED) was used to examine the effect of treatment (alginate vs. control) and time (0, 1 and 2 weeks), and their effect on body weight, waist circumference and taste preferences with sex and baseline body weight as covariates. Post hoc pair-wise comparisons were made using Tukey Kramer’s adjustment when the main analysis indicated a significant treatment effect. Additionally post hoc analysis with poor compliers removed defined as subjects consuming less than 85% of the preload beverages were conducted. The Wilcoxon signed rank sum test was used to examine differences between treatment groups in relation to compliance, frequency of self-reported adverse events and defecation (performed in PROC NPAR1WAY). Results A total of 20 subjects completed the pilot study, 12 in the alginate group and 8 in the control group. Four participants from the alginate group dropped out during the first week; three due to dislike of the
M. Georg Jensen et al. / Appetite 57 (2011) 601–604 Table 1 Compliance (%) for preload consumption over the 2-week intervention period (n = 20). No, I did not consume the preload beverage
I only drank some of the beverage
Breakfast preload Alginate 18.5%*** 4.7% Control 3.6% 0.0% Lunch preload Alginate 10.7%** 2.4% Control 0.0% 0.0% Dinner preload Alginate 5.3%* 4.2% Control 0.9% 0.0% Overall compliance (total of all three preloads) Alginate 11.5% 3.8% Control 1.5% 0.0%
Yes, I consumed the hole preload beverage 76.8% 96.4% 86.9% 100.0% 90.5% 99.1% 84.7%*** 98.5%
% calculation are within the groups (=rows). P-value for difference between groups: *P = 0.01, **P = 0.002, ***P = 0.0001.
preload beverage and one because of gastrointestinal discomfort. Baseline body weight (103.4 14.0 kg), BMI (33.8 3.3 kg/m2), waist circumference (106.6 9.0 cm) and age (35.7 7.5 years) did not differ between the two groups (P > 0.1). Compliance and palatability As shown in Table 1, we found an effect of time (P = 0.04) and treatment (P = 0.0001) on self-reported overall compliance, with 85% of subjects in the alginate group answering yes to the question ‘‘Did you drink the preload beverage today?’’ at the end of the 2week intervention compared to 98% in the control group. The lower compliance in the alginate group seems to be a result of difficulties with consumption of the breakfast preload (see Table 1). When analysing the individual compliance of the 20 subjects who completed the intervention, three subjects in the alginate group had a poor compliance with less than 85% of preload consumed. All subjects in the control group had a compliance >95%. The ratings on preload palatability were collected three times over the 2-week intervention period, with no effect of time observed (P = 0.2). However, there was a treatment effect on overall palatability with a slightly higher (and thereby worse) taste rating of the alginate-based preload (3.4 0.1 points) compared to control (3.0 0.1 points) (P = 0.05). Difference in palatability between groups did not change after exclusion of poor compliers. Anthropometry After 2 weeks, we observed a decrease in body weight in both groups (P = 0.02); however, this weight loss did not differ between groups ( 1.42 0.38 kg vs. 1.56 0.21 kg in the alginate and control group, respectively) (P = 0.4). When analyzing weight loss data after poor compliers (<85%) had been removed, the alginate group now exhibit a greater numerical decrease of 1.95 0.33 kg in body weight compared to 1.56 0.21 kg in the control group, however this difference did not reach significance (P = 0.33). Additionally, waist circumference decreased in both groups (P = 0.001); but again, there was no difference between group means ( 1.82 0.9 cm vs. 2.56 1.0 cm for alginate and control group, respectively) (P = 0.2). Although non-significant, removal of poor compliers resulted in a numerical larger difference between waist circumference for the control group 2.56 0.4 cm compared to 1.06 1.0 cm in the alginate group (P = 0.19). Gastrointestinal adverse events The self-reported answers on overall well-being after preload consumption during the 2 weeks revealed that 41% in the alginate
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group versus 58% in the control group felt ‘very well’ (P = 0.005). In addition, more subjects from the alginate group (17%) felt ‘moderately well’ after preload consumption compared to 4% in the control group (P = 0.001). When analysing well-being without the three poor compliers from the alginate group the difference in feeling ‘very well’ was no longer significant between groups (51% vs. 58% for alginate and control, respectively) (P = 0.25). No change in the results on feeling ‘moderately well’ was observed after removing poor compliers. We found an effect of treatment on self-reported adverse events, with higher frequency (13%) of a weak degree of diarrhoea after consumption of the alginate-based preload compared to control (1%) (P = 0.0001). The control group reported a higher frequency of a weak degree of constipation (13% vs. 2%, P = 0.007) and a moderate degree of flatulence (17% vs. 5%, P = 0.007) compared to the alginate group. No difference between groups was found in any of the other specific adverse events. No change in the results on self-reported adverse events was observed after removing poor compliers. During the intervention, we found a time (P = 0.005) and treatment effect (P = 0.04) on faeces texture, as 47% in the alginate group answered that their faeces had a more ‘loose’ texture compared to 16% in the control group. Frequency of defecation did not differ between groups (P = 0.3). No change in the results on faeces texture was observed after removing poor compliers. Discussion Our hypothesis was that alginate fibre as an adjuvant to a modest energy-restricted diet could improve body weight loss in obese subjects. However, no difference in weight loss or waist circumference was observed between groups during the 2-week study period, while compliance to preload consumption as well as palatability ratings differed between groups. We have previously shown that consumption of this alginate preload affected satiety, hunger feelings and energy intake in an acute meal test study (Jensen et al., 2011), although the observed reduction in ad libitum energy intake of the alginate preload in the acute study was modest ( 5%). However, if this effect could be extrapolated to a consistent decrease in energy intake by administration of three preloads daily, it is possible that such an energy deficit could affect the energy balance. We therefore anticipated that, if these suppressive effects on appetite occurred consistently during regular consumption, a larger decrease in body weight, beyond the modest energy-restricted diet, would be observed. After the post hoc analysis with poor compliers removed we found a numerical larger weight loss compared to the control group. However this was still non-significant, which could indicate that even when complying with the alginate treatment, no additional effect on weight loss could be produced. The lower compliance seen in the alginate preload group is probably related to the lower palatability of the preload. When we developed the preloads it was our aim to match the sensory properties; unfortunately, we were not successful in doing this, which is a limitation of the study. We did not collect information on sensory parameters such as mouth feel and texture of the preload; however we speculate that the lower compliance to consume the alginate beverage was perhaps due to the difference in preload viscosity. Even though the alginate beverage was based on a low-viscosity alginate, it still had a less attractive or perhaps ‘‘slimy’’ mouth feel compared to the control beverage. A decreased palatability of alginate formulations has also been reported by others (Hoad et al., 2004; Mattes, 2007), and it represents a recurrent challenge when adding viscous fibres to beverages. A possible reason for the lack of effect on body weight observed is the relatively small number of subjects enrolled and the short
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duration of the study, indicating that the study was underpowered to detect differences in body weight. In another shortterm study with 28 subjects that investigated the effect of a semisolid meal with or without added guar gum, a similar body weight loss over 2 weeks was found (Kovacs et al., 2001). This stresses that when investigating fibre supplementation and changes in body weight, longer duration of the intervention is required in order to detect a significant difference. However, it could be that alginate supplementation through suppression of hunger exhibits its effect as a better adherence to at hypo-caloric diet for a longer period of time. Therefore, it would be relevant to investigate whether consumption of alginate could act as an aid during lifestyle modifications such as changing eating behaviour with a view to losing weight. In conjunction to this, most studies investigating the effect of dietary fibre on appetite regulation, suggest that the type of fibre, amount and vehicle of administration are important (Kristensen & Jensen, 2011). A strong-gelling alginate with a high guluronic acid content added to a meal-replacement showed better hunger-reducing effect compared to weak-gelling alginates primarily based on mannuronic acid (Hoad et al., 2004). Additionally, it has been shown that adding alginate to liquid preloads had a greater effect on appetite control than adding alginate to a solid preload (Mattes, 2007; Paxman et al., 2008; Pelkman et al., 2007). Even though the preload beverages in our study were based on the highest amount of alginate administered to this date, we still relied on gastric acid secretion for gel formation. There are two approaches to alginate gel formation: (1) through acidification and (2) through divalent ion binding. When pH of the alginate solution is lowered beyond the pKa of the guluronic acid (3.65) and mannuronic acid (3.38), gel formation occurs due to protonation of the carboxyl groups by addition of inorganic acid. Addition of a divalent ion such as Ca2+ to the alginate solution results in a gel formation due to efficient ionbinding ability of alginate (Draget et al., 2000). If our preload formulation had been fortified with Ca2+, we would likely have gel formation in the stomach independent of pH. This could point to that addition of multivalent cations is highly needed for sufficient gel formation when developing alginate formulations for dietary supplementation. Monitoring of overall well-being during the 2-week intervention period showed that this specific alginate was moderately acceptable to the majority of subjects. This observation is in line with earlier acute studies on alginate consumption assessing gastrointestinal comfort (Mattes, 2007; Pelkman et al., 2007; Williams et al., 2004; Wolf et al., 2002). It has been suggested that alginate fibres are more slowly fermented than other viscous fibres (Brownlee et al., 2005), which might make alginate a better tolerated fibre source than rapidly fermented fibres that are often associated with discomfort in the gastrointestinal region. Nevertheless, as no significant difference in gastrointestinal adverse event between groups was found after post hoc analysis after removal of poor compliers, this could indicate that some subjects did not adhere to the alginate supplementation because it reduced their feelings of well-being or that tolerability differs between individuals, which perhaps depend on their habitual dietary fibre intake. One subject dropped out due to diarrhoea, which also was
the adverse event reported most frequently a weak degree of discomfort after alginate consumption compared to control and a higher percentage reported loose stool in the alginate group compared to control. However the term ‘loose stool’ was not defined as diarrhoea in the guiding to the subjects, which possibly could reflect that the subjects merely experienced less constipation or a softer defecation. Based on these findings a continuous monitoring of gastrointestinal discomfort is advisable in future studies. In conclusion, the alginate-based preload beverage did not produce additional weight loss in obese subjects beyond that resulting from the calorie-restricted diet. However, this is possibly due to limitations of study design and that the alginate formulation was reliant only on gastric acid for gel formation followed consumption. Our findings further indicated that alginate supplementation for 2 weeks was moderately acceptable to the majority of subjects, but a few subjects did not tolerate the supplementation leading to a lower compliance of preload consumption. Whether long-term alginate supplementation could be a potential aid for improving adherence to caloric-restricted diet for weight loss still requires further research. References Brownlee, I. A., Allen, A., Pearson, J. P., Dettmar, P. W., Havler, M. E., Atherton, M. R., et al. (2005). Alginate as a source of dietary fiber. Critical Reviews in Food Science and Nutrition, 45(6), 497–510. Dettmar, P. W., Strugala, V., & Craig Richardson, J. (2011). The key role alginates play in health. Food Hydrocolloids, 25(2), 263–266. Draget, K. I., Strand, B., Hartmann, M., Valla, S., Smidsrod, O., & Skjak-Braek, G. (2000). Ionic and acid gel formation of epimerised alginates; the effect of AlgE4. International Journal of Biological Macromolecules, 27(2), 117–122. Hoad, C. L., Rayment, P., Spiller, R. C., Marciani, L., Alonso, B. C., Traynor, C., et al. (2004). In vivo imaging of intragastric gelation and its effect on satiety in humans. Journal of Nutrition, 134(9), 2293–2300. Howarth, N. C., Saltzman, E., & Roberts, S. B. (2001). Dietary fiber and weight regulation. Nutrition Reviews, 59(5), 129–139. Jensen, M. G., Kristensen, M., Belza, A., Knudsen, J. C., & Astrup, A. (2011). Acute effect of alginate-based preload on satiety feelings, energy intake and gastric emptying rate in healthy subjects. Obesity, doi:10.1038/oby.2011.232 [Epub ahead of print]. Kovacs, E. M., Westerterp-Plantenga, M. S., Saris, W. H., Goossens, I., Geurten, P., & Brouns, F. (2001). The effect of addition of modified guar gum to a low-energy semisolid meal on appetite and body weight loss. International Journal of Obesity Related Metabolic Disorders, 25(3), 307–315. Kristensen, M., & Jensen, M. G. (2011). Dietary fibres in the regulation of appetite and food intake. Importance of viscosity. Appetite, 56(1), 65–70. Mattes, R. D. (2007). Effects of a combination fiber system on appetite and energy intake in overweight humans. Physiology & Behavior, 90(5), 705–711. Odunsi, S. T., Vazquez-Roque, M. I., Camilleri, M., Papathanasopoulos, A., Clark, M. M., Wodrich, L., et al. (2009). Effect of alginate on satiation, appetite, gastric function, and selected gut satiety hormones in overweight and obesity. Obesity Silver.Spring: . Paxman, J. R., Richardson, J. C., Dettmar, P. W., & Corfe, B. M. (2008). Daily ingestion of alginate reduces energy intake in free-living subjects. Appetite, 51(3), 713–719. Pelkman, C. L., Navia, J. L., Miller, A. E., & Pohle, R. J. (2007). Novel calcium-gelled, alginate-pectin beverage reduced energy intake in nondieting overweight and obese women: interactions with dietary restraint status. American Journal of Clinical Nutrition, 86(6), 1595–1602. Schofield, W. N. (1985). Predicting basal metabolic rate, new standards and review of previous work. Human Nutrition-Clinical Nutrition, 39(Suppl. 1), 5–41. Slavin, J. L. (2005). Dietary fiber and body weight. Nutrition, 21(3), 411–418. Williams, J. A., Lai, C. S., Corwin, H., Ma, Y., Maki, K. C., Garleb, K. A., et al. (2004). Inclusion of guar gum and alginate into a crispy bar improves postprandial glycemia in humans. Journal of Nutrition, 134(4), 886–889. Wolf, B. W., Lai, C. S., Kipnes, M. S., Ataya, D. G., Wheeler, K. B., Zinker, B. A., et al. (2002). Glycemic and insulinemic responses of nondiabetic healthy adult subjects to an experimental acid-induced viscosity complex incorporated into a glucose beverage. Nutrition, 18(7–8), 621–626.