1. Top of page
  2. Abstract
  3. References

MELA, DAVID J. Novel food technologies: enhancing appetite control in liquid meal replacers.

Several studies using a liquid meal replacement (MR)1 for weight management have demonstrated effective (7% to 8%) (1, 2) and sustainable (4 and 5 years) (3, 4) weight loss with concomitant improvements in weight-related risk factors of disease. Although MRs such as Slim·Fast (Unilever North America, Englewood Cliffs, NJ) have been repeatedly proven efficacious for weight management, consumer research has highlighted the need to better control hunger to enhance and sustain compliance in maximizing weight loss success. According to recent market research in the United States, the majority (53%) of respondents claim to cheat on a diet because they are hungry, and almost one in three (31%) feel that they are starving themselves while dieting (unpublished data, The Segmentation Company, a division of Yankelovich, Inc., Chapel Hill, NC). This section of the proceedings describes the development process of a novel food technology intended to increase satiety in MR products.

The guiding principle of the industrial research program has been to use the scientific literature to identify potential physiological targets and processes linked to satiety and then consider the range of technical routes that could be used to stimulate these. The research has made extensive use of in vitro gut models of varying complexity, which serve as a screening tool to select and test materials before testing in human subjects. Human testing has been used as a tool to understand mechanisms and confirm proof-of-principle (e.g., (5, 6)) and to confirm the effects and support claims in actual product formulations.

One of the initially identified targets for the satiety research program was the concept of the ileal brake. Dietary fat is usually digested and absorbed in the duodenum. However, it has long been known that if digestion and absorption of fats takes place in the distal sections of the small intestine digestion, this stimulates a strong feedback signal associated with slowing of gastrointestinal transit and release of various satiety hormones (7, 8, 9, 10). Thus, the digestion of fat in the ileum applies a brake on the digestive processes and intake behavior, as illustrated in Figure 1.


Figure 1. Intestinal model depicting the concept of the ileal brake.

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An important question for the research team was whether the ileal brake could function in the context of liquid MRs, which have a relatively low fat content. If activating the ileal brake required addition of substantial amounts of fat to products, the increase in energy density and content would probably defeat any possible advantage gained from stimulating the ileal brake. Proof-of-principle experiments were, therefore, designed to test for the activation of the ileal brake with low levels of lipids. As part of one experiment, volunteers were given a liquid MR at 0 hours, followed 105 minutes later by an ileal infusion of 3 grams of oil (experimental day) or saline (control day) for 45 minutes.

One of the key outcomes of the study was hunger and satiety ratings based on a 100-mm visual analog scale. This research showed that 3 grams of lipid delivered directly to the ileum caused a significant increase in self-reported satiety (Figure 2) (5). Secondary measures in that study showed that the group receiving 3 grams of lipid in the ileum also had an increase in cholecystokinin in the 3rd and 4th hours after ingestion of the MR drink. Cholecystokinin is a hormone that has been associated with hunger suppression in response to the presence of fats. Additional data showed that the ileal fat infusion also led to a reduced food intake in a later ad libitum test meal.


Figure 2. Satiety profile during stimulation of the ileal brake by intestinal infusion of lipid vs. saline (control). Subjects were fed a Slim·Fast meal replacer at time = 0 hours. This was followed from time = 105 to 150 minutes by ileal infusion of a total of 3 grams (i.e., 0.067 g/min) fat or saline control. Satiety was measured using a 100-mm line scale. The ileal brake is observed as distinct rise in the satiety response occurring during the fat (but not saline) infusion.

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Once it was shown that the ileal brake could in principle be activated by small amounts of fat, the next step was to refine the method of lipid delivery, test the optimal site of delivery and evaluate the physical characteristics of the lipid in the product to optimize effect. Studies confirmed that lipid placement in the ileum was superior to lipid placement in the duodenum and that the physicochemical properties of the lipid used were key.

Once clear evidence was available that the ileal brake was an effective and feasible target, the challenge was to stimulate this effect in a good-tasting, shelf-stable, nutritionally-balanced product formulation. The research team initially considered encapsulation of lipids to delay their digestion, allowing for activation of the ileal brake. However, this produced inconsistent results in clinical trials, and issues of cost and quality control of this approach also reduced the commercial viability. The focus shifted toward alternatives, particularly the use of emulsified lipid technology. Although there are many different aspects to consider in the composition and processing of lipid emulsions, the key issue for this research was how a liquid emulsion behaves under gastrointestinal conditions. Lipid emulsions were developed and assessed under in vitro conditions, which suggested that they could potentially improve appetite control via gastric and/or intestinal mechanisms. First, destabilization and the aggregation of lipid clusters under gastric conditions could delay emptying of fat from the stomach, possibly triggering early satiety hormone release with the start of the next meal. Second, slower rates of lipolysis under duodenal conditions could lead to delayed breakdown and delivery of lipid for digestion more distal in the small intestine.

Tests were done comparing a liquid MR with novel lipid emulsions under in vitro gastric conditions that consisted of 60-minute incubation with pepsin/lipase at 37 °C and an HCl-reduced pH of 1.8. We found that certain novel emulsions exhibit gastric aggregation of fat droplets in vitro, whereas the control (standard product) had no aggregation of fats at all. Gastric aggregates of the novel emulsions ranged in size from tens of micrometers to millimeter size (Figure 3).


Figure 3. Fat particle aggregation under gastric conditions with novel emulsion form of Slim·Fast liquid MR. Standard Slim·Fast Optima ready-to-drink and a novel emulsion form of Slim·Fast Optima ready-to-drink were incubated in gastric conditions (see text), and samples were removed and observed under a microscope, showing this differential aggregation of fat droplets.

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The next step of experimentation on these novel lipid emulsions was to determine the rate at which they would be processed in the intestine because stimulation of the ileal brake is dependent on the length over which lipids are hydrolyzed in the small intestine. Rates of intestinal lipolysis were measured by testing the liquid meal replacer with the novel emulsion under in vitro intestinal conditions. After processing the control and novel emulsion formulations using in vitro gastric conditions described above, the pH was raised to 7.5, and both bile extract and pancreatin were added to mimic intestinal conditions. It was found that the rate of lipolysis was significantly slower for the novel lipid emulsion formulation. Tests of the final product formulation containing the novel lipid emulsion technology showed that this produced a greater calorie-for-calorie satiety response than the original product and a consistent mean return to baseline for hunger and satiety responses of ∼4 hours.

Hunger control is seen as critical to the maintenance of a successful weight loss program. Over the last 5 years, a multidisciplinary undertaking by Unilever has taken physiological targets and translated them into technical targets, resulting in new proprietary product innovations. Future directions for this research program include further clinical testing and replication of the novel emulsion technology to extend and improve on the current results, clear resolution of the mechanism(s) and optimal conditions for novel emulsion action, and assessing possible combinations with other satiety or weight control technologies.

  • 1

    Nonstandard abbreviation: MR, meal replacement.


  1. Top of page
  2. Abstract
  3. References
  • 1
    Anderson, J. W., Konz, EC (2005) The use of very-low-calorie diets (VLCDs) and meal replacements for weight control. In Mela, D. (eds.). Food, Diet and Obesity. Woodhead Publishing Limited: Cambridge, United Kingdom. 379411.
  • 2
    Heymsfield, S. B., van Mierlo, C. A., van der Knaap, H. C., Heo, M., Frier, HI (2003) Weight management using a meal replacementstrategy: meta and pooling analysis from six studies. Int J Obes. 27: 537549.
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  • 4
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  • 5
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  • 6
    Hoad, C. L., Rayment, P., Spiller, R. C., et al (2004) In vivo imaging of intragastric gelation and its effect on satiety in humans. J Nutr. 134: 22932300.
  • 7
    Read, N. W., McFarlane, A., Kinsman, R. I., et al (1984) Effect of infusion of nutrient solutions into the ileum on gastrointestinal transit and plasma-levels of neurotensin and enteroglucagon. Gastroenterology. 86: 274280.
  • 8
    Spiller, R. C., Trotman, I. F., Higgins, B. E., et al (1984) The ileal brake: inhibition of jejunal motility after ileal fat perfusion in man. Gut. 25: 365374.
  • 9
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  • 10
    Welch, I., Saunders, K., Read, NW (1985) Effect of ileal and intravenous infusions of fat emulsions on feeding and satiety in human volunteers. Gastroenterology. 89: 12931297.