Fat digestion modulates gastrointestinal sensations induced by gastric distention and duodenal lipid in humans.

BACKGROUND AND AIMS: It is unclear whether fat digestion is required for the induction of gastrointestinal sensations and whether different fats have different effects. We investigated the effect of fat digestion and of medium-chain triglycerides (MCTs; C < 12) and long-chain triglycerides (LCTs; C > 16) on gastrointestinal sensations. METHODS: In a double-blind study, 15 healthy subjects were studied on 5 occasions during which LCT or MCT emulsions (2 kcal/min), with or without 120 mg tetrahydrolipstatin (THL, lipase inhibitor), or sucrose polyester (SPE, nondigestible fat) were infused intraduodenally in randomized order. After 30 minutes, the proximal stomach was distended in 1 mm Hg steps/min. Intensity of gastrointestinal sensations (on a 0-10 visual analog scale), plasma cholecystokinin (CCK) levels, and gastric volumes were assessed throughout. RESULTS: LCT and MCT increased gastric volume at baseline pressure compared with SPE, and LCT more than MCT. THL entirely abolished this effect (volumes [mL]: LCT, 213 +/- 19; LCT-THL, 39 +/- 3; MCT, 155 +/- 12; MCT-THL, 43 +/- 5; SPE, 44 +/- 5). Only LCT increased plasma CCK levels (pmol/L per 30 minutes: LCT, 21 +/- 2; LCT-THL, 9 +/- 1; MCT, 9 +/- 1; MCT-THL, 11 +/- 1; SPE, 9 +/- 1). During distentions, intragastric volumes were greater during infusion of LCT and MCT than during the respective THL conditions or SPE, but plasma CCK levels did not change. The intensity of sensations increased (hunger decreased) more with LCT than with MCT. During infusion of THL or SPE, the effects were smaller than during LCT or MCT. CONCLUSIONS: Fat digestion is required for the modulation of gastrointestinal sensations during gastric distention. The effects of fat depend on the fatty acid chain length and are not entirely explained by release of CCK.

Update on the pharmacotherapy of obesity.

OBJECTIVE: To review recent developments in the pharmacotherapy of obesity, including the agents currently approved for use in the management of obesity and those under development. DATA SOURCES: A MEDLINE search from January 1990 to July 1997 was conducted to identify English literature available on the pharmacotherapy of obesity. The search was supplemented by a review of the bibliographies of identified literature. STUDY SELECTION: All controlled and uncontrolled trials were reviewed. When available, double-blind, placebo-controlled trials were used preferentially. DATA EXTRACTION: Agents were reviewed with regard to mechanism of action, clinical trial data regarding efficacy, adverse effects, pharmacokinetics, drug interactions, and contraindications where information was available. Study design, selected population, results, and adverse effect information were included. DATA SYNTHESIS: The anorexiants currently available or under development for the management of obesity regulate food intake and satiety via the adrenergic and/or serotonergic pathways. Clinical trials have shown a 10-15% weight loss can typically be anticipated; however, little long-term safety and efficacy data are available. Adverse events tend to be mild and self-limiting, but serious adverse events can occur. Treatment options under development include thermogenic agents, digestive inhibitors, and analogs and antagonists of hormones that regulate food intake and satiety. CONCLUSIONS: Several mechanisms to control weight are currently under investigation for the management of obesity. Since obesity is a chronic condition, further studies should be conducted to evaluate the long-term safety and efficacy of these agents and the role of combination therapy using different modalities.

Review article: olestra and its gastrointestinal safety.

Olestra is a fat substitute made from sucrose and vegetable oil. Olestra is neither digested nor absorbed, and therefore adds no calories or fat to the diet. Because the gut is the only organ that is exposed to olestra, the potential for olestra to affect gastrointestinal structure and function, and the absorption of nutrients from the gut, has been investigated. Histological evaluations performed after long-term feeding studies have shown no indications that olestra causes injury to the gastrointestinal mucosa. Olestra is not metabolized by the colonic microflora, and has no meaningful effects on the metabolic function of these organisms. Studies of gastrointestinal transit have shown that the consumption of olestra with food does not affect gastric emptying, or small or large bowel transit times. Olestra does not affect the absorption of macronutrients, water-soluble vitamins or minerals. It causes a dose-responsive decrease in the availability of the fat-soluble vitamins A, D, E and K; however, this potentially adverse effect is offset by the addition of vitamins to olestra-containing foods. Olestra has no consistent effect on the amount of total bile acids excreted in the faeces, and therefore probably has no significant effect on bile acid absorption. The occurrence of gastrointestinal symptoms, including diarrhoea, loose stools, gas and abdominal cramping, after consumption of olestra under ordinary snacking conditions is comparable to that following consumption of triglyceride-containing snacks.

Assessment of the nutritional effects of olestra, a nonabsorbed fat replacement: introduction and overview.

Olestra is a mixture of polyesters formed from sucrose and fatty acids derived from edible fats and oils. It is not absorbed or digested and can serve as a zero-calorie replacement for dietary fat. Because olestra is lipophilic and not absorbed, it has the potential to interfere with the absorption of other dietary components, especially lipophilic ones, when it is in the digestive tract with those components. A series of studies were conducted in the domestic pig and in healthy adult humans to define the nature and extent of olestra's effect on fat-soluble vitamins, selected water-soluble micronutrients, and macronutrients, and to demonstrate that the effects of olestra on the absorption of fat-soluble vitamins can be offset by adding extra amounts of the affected vitamins to olestra foods. Before conducting the human and pig studies, the intake of olestra from the consumption of snack foods made with olestra was estimated for various subgroups. The potential for olestra to affect the absorption of nonessential but potentially beneficial dietary phytochemicals was also assessed. In addition, an assessment of how consumption patterns influence the effect of olestra on the absorption of the highly lipophilic carotenoids was made. Finally, the results from the pig and human studies were used to assess the potential for olestra to affect the nutritional status of subgroups of the population who have particularly high nutrient needs or unique dietary patterns that may lead to large olestra-to-nutrient intake ratios.