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Following U.S. Food and Drug Administration (FDA) approval for the use of olestra, a noncaloric fat substitute (brand name Olean) in food snacks, the manufacturer agreed to provide safety updates on market experience to the FDA. However, guidelines for food product postmarketing surveillance (PMS) are not available and those typically used with medical products were only partly applicable. In modeling the Olean program, we drew from experience with consumer products and incorporated elements typical of medical product PMS. A cooperative effort was established with Olean snack manufacturers and a two-tiered, multidisciplinary approach enlisting Consumer Relations and Medical Affairs personnel was used to maximize use of specialized skills. The result of this effort was implementation of a reliable PMS system which could handle a high volume of reports from consumers while providing pertinent data required for medical interpretation of these reports. Summaries of data for the Olean snack manufacturers and FDA were generated in timely fashion. In addition to collection of the spontaneous reports from consumers, a clinical studies program was undertaken and an independent medical advisory panel was established. Through these, we gained perspective on the spontaneous reports and additional confirmation of the safety of olestra in savory snacks.

Market introduction of savory snacks containing olestra offered an opportunity to evaluate the safety of olestra in a free-living population and thereby compare the outcome to the previously established safety profile determined in clinical trials in which subjects were required to eat predetermined amounts at prescribed intervals. Therefore, a multifaceted postmarketing surveillance program was designed to evaluate consumer experience and safety of olestra in the marketplace. Customer comments were solicited through toll-free telephone numbers. Collected data were evaluated by both internal and external medical experts. About 10% of toll-free telephone calls reported health effects, most of which were gastrointestinal (GI) in nature. Clinical studies were designed and conducted to determine potential GI effects under the range of consumption patterns reported by toll-free calls. Health effects reported were those found commonly in the general population and analyses of the data found no biological reason to conclude that serious or meaningful health effects were the result of olestra consumption.

The aim of this study was to determine the effects of olestra and sorbitol consumption on three accepted objective measures of diarrhea (stool output >250 g/day, liquid/watery stools, bowel movement frequency >3/day), and how stool composition influences reports of common gastrointestinal symptoms. A double-blind, placebo-controlled study compared the effects of sorbitol (40 g/day in candy), a poorly absorbed sugar-alcohol with known osmotic effects, with those of olestra (20 or 40 g/day in potato chips), a nonabsorbed fat, on objective measures of stool composition and GI symptoms. Sixty-six subjects resided on a metabolic ward for 12 days: 2 days lead-in, 4 days baseline, 6 days treatment. Sorbitol 40 g/day resulted in loose/liquid stools within 1-3 h of consumption. In contrast, olestra resulted in a dose-responsive stool softening effect after 2-4 days of consumption. Subjects reported "diarrhea" when mean stool apparent viscosity (peak force (PF), g) decreased from a perceived "normal" (mean +/- SE, 1355 +/- 224 g PF; firm stool) to loose (260 +/- 68 g PF) stool. Mean apparent viscosity of stool during treatment: placebo, 1363 +/- 280 g (firm); olestra 20 g/day 743 +/- 65 g (soft); olestra 40 g/day, 563 +/- 105 g (soft); and sorbitol 40 g/day, 249 +/- 53 g (loose). Of the 1098 stool samples collected, 38% (419/1098) were rated by subjects as "diarrhea," yet only 2% of treatment days (all in the sorbitol treatment group) met commonly accepted criteria for a clinical diarrhea. Sorbitol, but not olestra, increased the severity of abdominal cramping, urgency and nausea compared to placebo. Olestra consumption, at levels far in excess of normal snacking conditions, resulted in a gradual stool softening effect after several days of consumption, did not meet any of the three objective measures of diarrhea, and did not increase GI symptoms. Sorbitol consumption, at only 80% of the dose requiring a "laxative effect" information label, resulted in rapid onset loose/liquid stools and a significant increase in abdominal cramping, urgency and nausea. Overall, subjects categorized stool as "diarrhea" when stool decreased from their perceived "normal," but the vast majority of these reports were not associated with clinically significant diarrhea.

The prevalence and impact of abdominal pain, bloating, and diarrhea in the adult US population are largely unknown. We conducted a national, cross-sectional, telephone survey of US households to provide estimates of the frequency, duration, severity, and impact of specific digestive symptoms during the previous month. A total of 2510 subjects completed interviews (70.7% response rate). Among the respondents, 1017 (40.5%) reported one or more digestive symptoms within the month before the interview, including abdominal pain or discomfort 21.8%, bloating or distension 15.9%, and diarrhea or loose stools 26.9%. Women were more likely than men to report abdominal pain or discomfort (24.4% vs 17.5%) and bloating or distension (19.2% vs 10.5%), but not diarrhea or loose stools (27.1% vs 26.7%). Symptoms were less common among those ≥60 years of age. More than 65% of respondents rated symptoms as moderate or severe in intensity, and the majority reported limitations in daily activities. We conclude that digestive symptoms are more common than previously recognized and have a significant impact.

PURPOSE: To determine the effects of olestra, a zero-calorie fat substitute that is neither digested nor absorbed, on the well-being and disease state of persons with chronic inflammatory bowel disease (IBD) in remission. PATIENTS AND METHODS: Eighty-nine patients with mild to moderate ulcerative colitis (n = 43) or Crohn's disease (n = 46) in remission, with a history of disease of 2 years or longer, were enrolled in this prospective study from nine private practices, three university-based medical centers, and one Veterans Administration medical center in the United States. Forty-four patients were randomly assigned to receive olestra and 45 to receive triglycerides in chips or cookies daily for 4 weeks. At Week 4, patients were classified as in remission, worsened, or relapsed according to an investigator's global assessment based on sigmoidoscopy (for ulcerative colitis) or the Crohn's disease activity index, laboratory findings, and clinical course. RESULTS: At Week 4, the olestra and triglyceride groups did not differ significantly with respect to the percentages of patients who relapsed ( P = 0.494; difference=2.4%; upper 95% CL=8.8%) or with respect to the percentages of patients who experienced any worsening of their symptoms ( P = 0.630; difference=0.2%; upper 95% CL=13.3%). Of evaluable patients, 90% (37 of 41) given olestra remained in remission with no worsening, compared with 90% (38 of 42) given triglycerides. Gastrointestinal symptoms were comparable between the treatment groups, and there were no treatment-related laboratory abnormalities. Six patients were excluded from analysis for reasons unrelated to treatment. CONCLUSION: Olestra did not affect the activity of quiescent mild to moderate IBD.

Groups of weanling pigs were fed a purified diet containing graded concentrations of olestra ranging from 1.1 to 7.7% (wt/wt) and the NRC's requirements for micronutrients for 12 wk. Each group consisted of 12 pigs, with the exception of the control group, which had 20, with equal numbers of females and castrated males. The purpose of the study was to determine the dose-response effects of olestra on fat-soluble vitamins and selected water-soluble micronutrients. At wk 0, 4, 8 and 12, hematology, clinical chemistry and blood concentrations of vitamins A, E, K and B12, and 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, folate, calcium, iron, zinc and adipose concentration of vitamin E were measured. Cumulative weight gain and feed efficiency were determined weekly. Prothrombin time was measured weekly for the control group and the groups fed 5.5 or 7.7% olestra, and monthly for other groups. Liver concentrations of vitamins A, E, and B12 and iron and bone concentrations of calcium, phosphorus, zinc and ash were measured for 12 pigs killed at wk 0 and for all animals at wk 12. By wk 12, the pigs were eating from 20 to 155 g/d of olestra. Olestra did not affect the pigs' growth or feed efficiency, indicating that the digestion and absorption of macronutrients were unaffected. Olestra reduced tissue concentrations of vitamin A, vitamin E and 25-hydroxyergocalciferol in a dose-responsive manner but did not affect prothrombin time. Olestra had no effect on the status of folate, vitamin B12, zinc or iron. Statistically reduced liver concentrations of vitamin B12 and iron in groups fed 5.5 or 7.7% olestra and a significant trend in bone ash content with olestra intake were possibly due to the poor vitamin A and/or vitamin E status of the pigs.

The effect of olestra, a zero-calorie fat replacement, on the absorption of dietary fat was determined with a dual-isotope technique in 67 healthy male subjects. After a 30-d adaptation period in which they consumed potato chips which delivered either 10 g/d olestra or 10 g/d triglyceride under free-living conditions, the subjects were housed in a metabolic ward and given 0, 8, 20 or 32 g olestra in potato chips. The chips were eaten as part of a breakfast containing about 38 g of fat, about 0.16 mg of 14 C-triolein, and a nonabsorbable marker, 51 CrCl 3 . Feces were collected for 7 d, and aliquots of the two daily collections containing the highest levels of 51 Cr were oxidized. The CO 2 was collected, and 14 C content was determined by liquid scintillation spectrometry. The fractional absorption of 14 C-triolein was calculated from the average ratios of 14 C/ 51 Cr dosed and measured in the feces. Olestra had a slight but significant dose-response effect on triglyceride absorption: the highest olestra dose (32 g) reduced absorption by 1.2%. This effect is not nutritionally significant with respect to either availability of essential fatty acids or energy intake.

Olestra is a zero-calorie fat substitute that is neither digested nor absorbed. A randomized, double-blind, placebo-controlled, within-subject, crossover rechallenge study was conducted to compare the occurrence of gastrointestinal symptoms after ingestion of chips made with Olean brand of olestra or conventional triglycerides in subjects who had previously experienced gastrointestinal symptoms they attributed to consuming Olean. A total of 57 male or female subjects received 2 oz of Olean potato chips or triglyceride potato chips at each of four weekly site visits. The occurrence of gastrointestinal effects after product consumption was noted in follow-up telephone interviews 3 to 5 days after each visit. There was no significant difference in the frequency of any gastrointestinal symptoms (abdominal cramping, diarrhea, loose stools) following consumption of Olean chips or triglyceride chips, and the severity of diarrhea, loose stools, and abdominal cramping was similar. We conclude that consumption of a 2-oz serving of Olean chips is no more likely to result in reports of gastrointestinal symptoms than consumption of triglyceride snacks as a part of the usual diet, even in individuals who have claimed intolerance to Olean. The data suggest that subjects who previously experienced symptoms that they attributed to consuming products made with Olean may have mistakenly attributed their symptoms to these products.

One hundred two normal healthy males and females were given 0, 8, 20 or 32 g/d olestra to which had been added graded amounts of vitamins A, D and E for 8 wk in a parallel, double-blind study. The primary purpose of the study was to determine the amounts of vitamins D and E needed to offset the effect of olestra on the availability of these vitamins. Serum concentrations of retinol, carotenoids, 25-hydroxyvitamin D metabolites, alpha-tocopherol, phylloquinone, lipids, ferritin and total iron, iron-binding capacity and hematology parameters, plasma concentrations of des-gamma-carboxyprothrombin and prothrombin, and urinary gamma-carboxyglutamic acid (Gla) excretion were measured biweekly. Clinical chemistry and urinalysis parameters, vitamin B12 absorption, and serum 1,25-dihydroxyvitamin D concentration were measured at wk 0 and 8. Serum concentrations of alpha-tocopherol and 25-hydroxyergocalciferol were restored to control concentration by adding 2.1 mg d-alpha-tocopheryl acetate and 0.06 microg ergocalciferol per gram of olestra, respectively, to the diet. Olestra reduced serum concentrations of 25-hydroxyergocalciferol, carotenoids and phylloquinone in a dose-responsive manner but did not affect Gla excretion, plasma des-gamma-carboxyprothrombin and prothrombin concentrations, overall vitamin D status, vitamin B12 absorption or iron status. Laboratory evaluations showed no olestra-related effects. Subjects in all groups reported mild to moderately severe transient gastrointestinal symptoms. These symptoms did not affect study compliance or the integrity of the data.

This study examined the effect of olestra, a zero-calorie fat replacement, on the absorption of retinyl palmitate in humans. After a 30-d adaptation period during which they consumed 10 g olestra/d in potato chips under free-living conditions, 68 healthy male subjects were housed in a metabolic ward and given a single dose of retinyl palmitate (0.33 RDA) containing a trace amount of 3H-retinyl palmitate with a breakfast that contained 0, 8, 20 or 32 g of olestra and about 38 g of triglyceride. Blood was collected at defined intervals for 48 h and plasma analyzed for 3H-retinyl esters by HPLC and liquid scintillation spectrometry. There was no significant effect on retinyl palmitate absorption as determined from the area under the plasma 3H-retinyl esters concentration-time curve. However, an area under the plasma concentration-time curve in the 32-g olestra group that was 81% (mean value) or 70% (median value) of the area under the curve for the placebo group suggested that olestra may have affected retinyl palmitate absorption. Inclusion or exclusion of 13 high responders did not change the results.

BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.

Background: Olestra is a new fat replacement that adds no calories to food. Because olestra is neither digested nor absorbed it has the potential for GI symptoms. We conducted a randomized, double-blind trial to determine the true incidence and impact of GI symptoms in free-living adults and children consuming olestra snacks ad libitum. Methods: 3,181 participants were randomized by household and consumed either olestra or regular full fat potato and corn chips in olestra-labeled packages. Participants could also choose additional full fat snacks in commercial packages. A household representative visited one of two central sites weekly, for 6 weeks, to select snacks and to return daily diaries. Each subject in the study recorded daily the amount of snacks consumed, GI symptoms, and the impact of symptoms on activities. Results: A total of 2,296 teens and adults (ages 13-89) and 885 children (ages 2-12) consumed test snacks during the study. There was no overall difference in GI symptoms. Of 1,620 individuals in the olestra group, 619 (38.2%) reported one or more GI symptoms, compared to 576 (36.9%) of the 1,561 individuals consuming full fat snacks, p=0.60. There were also no significant differences between the olestra and full fat groups in the incidence of any one of 8 GI symptoms, except for increased nausea in the full fat group (Table). Mean number of symptom-days were not different between groups for any of the 8 GI symptoms, except for "more frequent bowel movements" (3.7 vs 2.8 days, olestra vs. full fat, p=0.04). There was no difference in the impact of symptoms on daily activities between the 2 groups. Of subjects who reported that they visited a physician for GI symptoms, 6 were in the olestra group and 10 in the full fat group. Test chips were consumed frequently throughout the study (mean 20.2 vs. 21.6 of 42 study days, for olestra and full fat). The frequency of consumption did not correlate with symptom reporting in either group.

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Context.—Olestra, a nonabsorbable, energy-free fat substitute used in snack foods, has been anecdotally reported to cause gastrointestinal (GI) adverse events, although such effects were not expected based on results from randomized trials, in which it was consumed in typical snack patterns.Objective.—To determine whether ad libitum consumption of potato chips made with the fat substitute olestra results in a different level of GI symptoms than regular chips made with triglyceride (TG).Design.—Randomized, double-blind, parallel, placebo-controlled trial.Setting.—A suburban Chicago, Ill, multiplex cinema.Subjects.—A total of 1123 volunteers aged 13 to 88 years.Intervention.—Subjects were given a beverage and an unlabeled, white 369-g (13-oz) bag of potato chips made with olestra or TG during a free movie screening.Main Outcome Measures.—Total and specific GI symptoms reported during a telephone interview conducted from 40 hours to 10 days after ingestion; level of potato chip consumption; and satiety level.Results.—Of 563 evaluable subjects in the olestra chip group, 89 (15.8%) reported 1 or more GI symptoms, while 93 (17.6%) of the 529 evaluable subjects in the regular TG chip group did so (difference in symptom frequency between olestra and TG, −1.8; 95% confidence interval, −6.2 to 2.7; P=.47). For specific GI symptoms (eg, gas, diarrhea, abdominal cramping), there were no significant differences between olestra and TG chips. Fewer olestra chips were consumed than TG chips (60 vs 77 g [2.1 vs 2.7 oz]; P

In this study we demonstrate that apolipoprotein A-I determined the common size classes of discoidal particles formed with numerous phosphatidylcholines, and with ether analogs of phosphatidylcholines. We show furthermore, that the nature of the lipids dictates the distribution of particles among the different size classes. These experiments were performed with discoidal complexes containing various phospholipids (phosphatidylcholines with saturated and unsaturated fatty acid chains of different lengths and the ether analog of 1-palmitoyl-2-oleoylphosphatidylcholine), cholesterol, and human apolipoprotein A-I, prepared by the sodium cholate dialysis method, and fractionated by Bio-Gel A-5m gel-filtration chromatography. The complex preparations were analyzed in terms of their average composition, spectral properties of the apolipoprotein, and the dynamic behavior of the lipid domains. Nondenaturing gradient gel electrophoresis was used to analyze the size classes of particles present in the complex preparations. Starting with reaction mixtures containing around 100:1, phospholipid/apolipoprotein A-I molar ratios, complexes were isolated with molar ratios from 40:1 to 100:1. In most complexes apolipoprotein A-I had high levels of α-helical structure (65–77% α-helix), and tryptophan residues in a nonpolar environment. The lipid domains of complexes exhibited the dynamic behavior expected of the main phospholipid components. In the average size range from 90 to 100 A diameters, discrete particle classes with 80, 87, 102, 108, or 112 A Stokes diameters were observed for all the complexes containing different phospholipids. These discrete, recurring particle sizes are attributed to distinct apolipoprotein A-I conformations and variable lipid content.