An extensive research program was conducted to assess the potential of olestra, a zero-calorie fat replacement, to affect nutritional status. Olestra (Olean, Procter & Gamble, Cincinnati, OH) is approved for use in replacing 100% of the cooking oil used in the preparation of savory snacks such as potato and corn chips and crackers (Federal Register 1996). Key studies conducted as part of this program are described in the preceding articles in this supplement. This paper provides an overall summary of the integrated findings from the program.

Because olestra is lipophilic, nondigestible and nonabsorbable, it has the potential to interfere with the absorption of other components of the diet, especially lipophilic ones, eaten at the same time as olestra. This interference occurs because a portion of those components may partition into the olestra in the gastrointestinal (GI)³ tract and be excreted with the olestra (Jandacek 1982). Because it is lipophilic, olestra is expected to interfere with the absorption of only lipophilic molecules by this mechanism; water-soluble substances do not partition into olestra. An important aspect of this partitioning mechanism is that it is a physical interaction that occurs in the lumen of the gut. Olestra does not affect the physiological processes involved in nutrient digestion, absorption and metabolism, as discussed in the introductory article in this supplement (Peters et al. 1997). Olestra has no effect on nutrient stores accumulated prior to the consumption of olestra (i.e., olestra does not deplete the body of nutrients), or the utilization of those stores, and any effect that olestra might have on nutritional status can be prevented by the addition of extra amounts of the affected nutrient to olestra foods.

Because olestra has this potential to affect the availability of certain dietary components, and thus nutritional status, an essential part of the overall evaluation of the safety of olestra included a thorough investigation of the potential effects of olestra on the availability of dietary components. The dietary components that were assessed included macronutrients, essential vitamins and minerals, and other components of the diet such as phytochemicals. The focus of the nutrition program was to determine to what degree olestra affected the absorption of key dietary components and how the effects could be offset.

The broad objectives of the olestra nutrition research program were as follows: 1 ) to define the nature and magnitude of olestra's effect on the absorption of the fat-soluble vitamins and other lipophilic dietary components; 2 ) to determine if the effects of olestra on the absorption of fat-soluble vitamins could be offset by adding the affected vitamins to foods containing olestra; and 3 ) to investigate whether olestra might interfere with the absorption or utilization of macronutrients or water-soluble micronutrients by a mechanism or mechanisms other than the partitioning mechanism. Other facets of the program included a determination of how much olestra people would ingest from eating olestra snacks, the frequency and context (with or without meals) of snack consumption, an assessment of the potential for olestra to affect the availability of dietary phytochemicals, and an assessment of the nutritional safety of olestra for subgroups of the population who might have either unique dietary patterns or unique nutritional needs.

APPROACH AND SCOPE OF THE PROGRAM

Clinical studies in adult male and female subjects were used to confirm and extend the results from the pig studies. For example, measurement of the effects of olestra on carotenoid absorption and on vitamin K function, using parameters that are more sensitive than clotting times, were made in the human studies as were the direct measurements of the effect of olestra on the absorption of triglyceride, vitamin A and vitamin B-12. In the human studies, olestra was provided in foods representative of its intended use, primarily in potato chips, and, as with the pig studies, the human studies were conducted with daily olestra intakes and eating frequencies that were extreme relative to real-life dietary patterns for savory snacks. In all human studies except one, a study in a free-living population, the diet and eating habits of the subjects were strictly controlled and monitored. In both human and pig studies, nutritionally or physiologically meaningful parameters that reflect overall status were measured when possible; in some cases direct measurements of absorption were made. Table 1 illustrates key design elements of the pig and human studies.

Table 1. Design elements of the olestra nutrition studies in the domestic pig or adult humans [View Table]

In addition to the pig and human studies, other studies or assessments were conducted to help place the results of the studies in perspective relative to real life, or to assess the potential effects of olestra on substances not included in the studies. An integral and important part of the program was a study that estimated potentially how much and how often people would eat olestra. Others studies estimated the magnitude of the effect of olestra on carotenoid absorption when olestra snacks and carotenoid-containing foods are eaten in real life and assessed the potential of olestra to affect the availability of dietary phytochemicals. Finally, the results from the pig and human studies were examined to determine their relevance to subgroups of the population who might have nutritional needs or dietary habits different than those of the subjects used in the studies.

SUMMARY AND DISCUSSION OF RESULTS

In contrast to these patterns, savory snacks are eaten by the average consumer five times in a 14-d period, and 8% of this consumption occurs with meals (Webb et al. 1997). At the 90th-percentile consumption level, snacks are eaten 10 times in a 14-d period; 18% of that consumption is with meals. Figure 1 compares the eating frequency used in the human studies with the eating frequency of individuals who consume snacks at various levels. In real life, most of an individual's nutrients will be consumed at times other than when olestra is eaten.

An additional exaggerating factor in the pig studies was the method of feeding olestra; it was mixed in the diet when the diet was prepared. This increases the opportunity for the olestra-nutrient interaction to occur and thus for olestra to affect absorption. The result of mixing olestra in the diet is illustrated by findings from a study in which pigs were fed the same amount of olestra either mixed in the diet or in potato chips (Daher et al. 1997a). The effects of olestra on the absorption of fat-soluble vitamins were 1.7-4.5 times greater, depending on the vitamin, when olestra was mixed in the diet relative to being fed in potato chips.

The daily olestra intakes used in the studies were also exaggerated in relation to estimated potential intakes of olestra. The mean chronic intake of 18- to 44-y-old adults, the age range covering the majority of the subjects in the studies, was estimated to be 3.7 g/d; the 90th-percentile intake was estimated to be 8.1 g/d. In the human studies, olestra doses as high as 32 g/d were used. Even more exaggerated intakes were used in the pig studies.

The effects of olestra on the absorption of dietary components observed in pigs and humans were consistent. In both kinds of studies, the results were consistent with the partitioning mechanism, a strong indication that this mechanism is the only significant mechanism by which olestra exerts an effect on nutritional status. Table 2 illustrates how the data from the human and pig studies were used to define the effects of olestra on water-soluble and fat-soluble nutrients.

Table 2. How data from the human and pig studies were used to accomplish the objectives of the program and define the effects of olestra on water-soluble and fat-soluble nutrients1 [View Table]

Olestra did not affect the digestion, absorption or utilization of macronutrients. This was evidenced by the fact that olestra did not affect growth or digestible energy intake of the pigs (Cooper et al. 1997a, 1997b and 1997c). Fat absorption was measured directly, and the small effect of olestra was not nutritionally significant (Daher et al. 1997c). Of the macronutrients, fat is the most lipophilic; its digestion and absorption involve processes (i.e., lipolysis and micelle formation) that are the most likely to be affected by olestra. Failure of olestra to affect fat absorption is important evidence that olestra does not affect the digestion or absorption of other macronutrients.

Vitamin A. Liver vitamin A concentration was reduced by about 45% in pigs fed 0.25% olestra (wt/wt) in a diet that provided about 75% of vitamin A as retinyl palmitate and about 25% as provitamin A carotenoids (Cooper et al. 1997b). A dietary olestra concentration of 0.25% is similar to the 90th-percentile chronic human intake from savory snacks, 6.9 g/d. Feeding olestra mixed in the diet increases the effect on liver vitamin A by about three times relative to the situation in which it is eaten as potato chips (Daher et al. 1997a), which means that, had the pigs been fed olestra in chips, the effect of 0.25% olestra on liver vitamin A concentration would have been a reduction of ~15%.

The dose response of olestra on liver vitamin A concentration in the pig was fully manifested during the 12-wk studies. Figure 2 compares 12-wk data (Cooper et al. 1997c) and 26-wk data (Cooper et al. 1997b). The magnitude of the effect did not change as the pigs aged through their most rapid growth period and sexual maturity.

At intakes likely to result from the consumption of olestra savory snacks, olestra does not significantly affect the absorption of preformed vitamin A (Daher et al. 1997b); therefore the reduction in liver vitamin A results primarily from a reduction in carotenoid absorption. In the 8-wk studies, 20 g/d olestra reduced the absorption of -carotene by ~58% (Schlagheck et al. 1997a and 1997b). Other carotenoids, with the exception of lutein, were similarly affected. The absorption of lutein, a less lipophilic carotenoid, was reduced by ~48%. In the 16-wk study in free-living subjects, 18 g/d olestra reduced the absorption of -carotene by ~27% (Koonsvitsky et al. 1997). In both the 8-wk and 16-wk studies, serum carotenoid concentrations declined rapidly after olestra ingestion was started and reached a new steady-state level in <4 wk. These results indicate that daily consumption of olestra may reduce the steady-state circulating concentrations of carotenoids but does not lead to depletion as occurs when people consume carotenoid-free diets. This is illustrated in Figure 3, which shows the change in serum carotenoids concentration, plotted as a percentage of the base-line value, observed in the 16-wk study (Koonsvitsky et al. 1997) and the change when subjects consumed a low-carotenoid diet, in this case <4 mg/d (Rock et al. 1992).

The amount of vitamin A required to offset the effect of olestra was determined from direct measurements of liver stores of the vitamin in pigs. The pigs were fed diets that provided vitamin A as a 3:1 ratio of retinyl palmitate and -carotene in terms of retinol equivalents. The amount of vitamin A required to offset the effects of olestra was found to be an essentially a linear function of the amount of olestra in the diet over the range of olestra tested, 1.1-7.7% (Cooper et al. 1997a). A 26-wk study, which tested dietary concentrations of olestra that encompassed estimated daily intakes of olestra by humans from savory snacks prepared with olestra, showed that restoration of liver vitamin A concentration to control required 93 µg retinyl palmitate/g olestra (Cooper et al. 1997b).

Because of the similarities between pig and human GI physiology and because the diet used in the pig studies modeled the human diet with respect to vitamin A sources and fat intake, the restoration result obtained in the pig for vitamin A is appropriate for humans. Further evidence of the appropriateness of the pig as a surrogate for humans comes from the data on vitamin E discussed below.

Vitamin E. The pig studies showed that serum and liver concentrations of vitamin E were similarly affected by olestra (Cooper et al. 1997b and 1997c). For pigs fed 0.25 or 0.5% olestra, liver vitamin E was reduced by 24 and 31%, respectively, and serum vitamin E was reduced by 26 and 49%, respectively (Cooper et al. 1997b). These dietary concentrations of olestra provided daily intakes that ranged from 4 to 10 g/d by the end of the study, intakes similar to the mean 90th-percentile human intake, 3.7-10.0 g/d, from savory snacks depending on gender or age (Webb et al. 1997). Results from a study in which pigs were fed olestra either mixed in the diet or in potato chips indicate that these effects on vitamin E status would have been ~50% less (i.e., 12-25%) had the pigs been fed olestra in potato chips (Daher et al. 1997a).

Data from pigs showed that the relationship between the amount of vitamin E required to maintain tissue concentrations at control concentrations and the amount of olestra in the diet was essentially linear, as was also true for vitamin A.

Restoration of serum vitamin E concentration to control level in the pig required 2.2 mg d--tocopheryl acetate (TA)/g olestra, and restoration of liver vitamin E concentration required 2.1 mg TA/g olestra (Copper et al. 1997a). The finding that serum and liver concentrations respond in the same way to olestra intake and to the addition of extra vitamin E to the diet was important because it supports the use of serum vitamin E as a measure of vitamin E status in humans.

In humans, 8 and 20 g/d olestra, eaten in potato chips, reduced serum vitamin E by ~6 and 18%, respectively, in reasonable agreement with the effects measured in the pig had the pigs been fed olestra in potato chips (Schlagheck et al.1997b).

The linear relationship between the amount of additional vitamin E required to restore serum vitamin E to control concentration and the amount of olestra in the diet was confirmed in humans, and it was found that 2.1 mg TA/g olestra was required to offset the effect of olestra (Schlagheck et al. 1997a). This value agrees with that found for the pig. The finding of similar restoration values for vitamin E in humans and pigs provides further evidence of the appropriateness of the pig model for establishing the restoration level for vitamin A in humans, for whom direct measures of vitamin A tissue stores cannot be made.

Vitamin D. The serum concentration of 25-hydroxyergocalciferol [25(OH)D₂] was used as a measure of the effect of olestra on the absorption of dietary vitamin D. In addition, serum concentrations of 25-hydroxycalcifereol [25(OH)D₃], total 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)₂D] were measured to provide an assessment of total vitamin D status. In the pig, bone concentrations of ash, calcium and phosphorus were also measured.

The combination of pig and human data showed how olestra affected circulating concentrations of the metabolites with different relative contributions of dietary vitamin D to total vitamin D status. Serum 25(OH)D₂ was reduced by 20-25% by olestra in humans, depending on olestra dose, and the effect was essentially the same in the absence and presence of a 20 µg/d supplement of ergocalciferol (Schlagheck et al. 1997a and 1997b). The supplement resulted in a dietary contribution of ~68% to total vitamin D status. In the nonsupplemented study, the dietary contribution was ~20%. Also, the effect of olestra on serum 25(OH)D₂ was essentially the same in pigs exposed or not exposed to UV light (Cooper et al. 1997a and 1997b).

The contributions of dietary vitamin D-2 to overall vitamin D status in these studies encompassed and exceeded the dietary contribution for the general population. The majority of people obtain <20% of their vitamin D from the diet (Haddad and Hahn 1973, Jones 1978, Jones et al. 1991). In more extreme climatic conditions, such as winter in Canada, the contribution of dietary vitamin D to overall status may be no more than 50% (Delvin et al. 1979).

Measures of overall vitamin D status such as serum 1,25(OH)₂D and 25(OH)D concentrations were not significantly affected by olestra in either the pig or the human studies, including the 16-wk human study in free-living subjects (Koonsvitsky et al. 1997).

The amount of vitamin D required to offset the effect of olestra was determined from the 8-wk human study (Schlagheck et al. 1997a). This study showed that 0.06 µg ergocalciferol/g olestra offset the effect of olestra on serum 25(OH)D₂ concentration.

Vitamin K. Both pig and human studies showed that olestra, at any of the intakes tested, did not affect vitamin K function. Neither prothrombin time (PT) nor partial thromboplastin time (PTT) was affected in pigs fed vitamin K near the NRC requirement for 12 wk (Cooper et al. 1997c) or about one fifth of the requirement for 39 wk (Cooper et al. 1997b). In humans, plasma concentrations of des--carboxyprothrombin and prothrombin, and urinary excretion of -carboxyglutamic (Gla) were used as measures of vitamin K function. Urinary Gla excretion reflects vitamin K-dependent carboxylation of glutamic acid residues in proteins produced by the liver and by other tissues; plasma des--carboxyprothrombin reflects incomplete carboxylation of plasma prothrombin. Both measures are considerably more sensitive to changes in vitamin K function than are clotting times (Suttie 1992). In the 16-wk human study, plasma concentration of functional prothrombin was measured (Simplastin-Ecarin assay). No significant changes were observed in any of these functional parameters.

Olestra did reduce serum phylloquinone concentration in humans by 36-47%, depending on dose (Schlagheck et al. 1997a and 1997b). However, changes in serum phylloquinone do not necessarily reflect changes in overall vitamin K status. Because the half-life of circulating phylloquinone is ~104 min, (Shearer et al. 1974), serum phylloquinone reflects mainly short-term intake of the vitamin. Evidence of this was found in the 8-wk dose-response study in which the subjects ate different amounts of phylloquinone on the days immediately before blood draws (Schlagheck et al. 1997b). The intake of phylloquinone on the day immediately before the four blood draws was 235, 43, 78 and 235 µg/d, respectively. Serum phylloquinone concentration for the control group (no olestra) at the four draws was 1.3 ± 0.13, 0.51 ± 0.13, 0.64 ± 0.07 and 1.6 ± 0.18 nmol/L, respectively.

The data from this study also allowed the amount of vitamin K required to offset the effect of olestra on serum phylloquinone to be calculated as follows. For each treatment group (0, 8, 20 or 32 g/d olestra) a best-fit linear regression equation describing the relationship between serum phylloquinone concentration and the previous day's vitamin K intake was derived. Then, the serum concentration of phylloquinone that would result from eating 80 µg [1 recommended dietary allowance (RDA)] of vitamin K in the absence of olestra was calculated from the equation derived for the control group, 0.69 nmol/L. As a next step, this value was inserted into the regression equations for the olestra groups, and the amount of vitamin K required to maintain serum phylloquinone at the control value in the presence of 8, 20 or 32 g/d olestra was calculated. These calculated values were then adjusted for the 1 RDA vitamin K intake by the control group by subtracting 80 µg from each. These calculations showed that 31, 68 and 82 µg of vitamin K were required to offset the effects of 8, 20 and 32 g/d olestra, respectively. These values were converted to µg/g olestra and averaged to produce a restoration value of 3.3 µg vitamin K/g olestra.

As part of the olestra approval process, the Food and Drug Administration (FDA) carefully considered the effects of olestra on the absorption of the fat-soluble vitamins. The studies, conducted under exaggerated dietary conditions as discussed above, showed no significant effects of olestra on overall vitamin D status or vitamin K function. Further, the effects of olestra on the absorption of vitamin A and vitamin E are likely to be small and not nutritionally significant for most people eating savory snacks made with olestra. However, the fat-soluble vitamins are essential nutrients, and there may be individuals whose dietary patterns would lead to larger effects than those measured in the test subjects, or individuals whose vitamin status is marginal or inadequate and in whom any decrease would therefore be undesirable. Because of these possibilities, the FDA concluded that the potential benefit of adding all four fat-soluble vitamins to olestra snacks in sufficient amounts to offset any olestra effects outweighed any potential risk from such additions (Federal Register 1996).

Addition of the required amounts of fat-soluble vitamins to olestra will pose no risk of vitamin toxicity. The added amounts of the vitamins, even if all were absorbed, are well below amounts known to product toxic effects (Federal Register 1996, Schlagheck et al. 1997a). Table 3 lists the vitamin addition levels recommended by the FDA in terms of recommended daily intakes (RDI) that would be contained in a single serving of olestra savory snacks, in this case a 1-ounce serving of potato chips, the snack food that would contain the greatest amount of olestra per serving, 10 g. The total amounts of added vitamins will not all be absorbed and, most importantly, the added vitamins simply maintain tissue concentrations at control values and do not increase them.

Table 3. The amounts of fat-soluble vitamins that will be added to savory snacks to offset the potential effects of olestra on the absorption of these vitamins. The amounts are expressed in terms of the recommended daily intakes (RDI) of the vitamins added to a single serving of savory snacks [View Table]

A further perspective on the importance of dietary pattern comes from comparison of the effects of olestra on the absorption of -carotene measured in the 8-wk studies and the 16-wk study with the effect calculated from real-life eating patterns of snack foods and carotenoid-containing foods (Cooper et al. 1997e). To what extent olestra might affect carotenoid absorption when people eat olestra snacks and carotenoid-containing foods in their habitual eating pattern was estimated as follows. First, analysis of menu census data showed that an individual eating savory snacks at the 90th-percentile level eats snacks and carotenoid-containing foods together about five times in a 14-d period. The intake of -carotene, used as a marker of carotenoid intake in general, was calculated for the general population from the menu census data. Then, the intake was recalculated assuming that the -carotene intake would be reduced by the amount measured in the 8-wk human studies each time a savory snack and a carotenoid-containing food were eaten together. The calculated average reduction in -carotene intake (all ages, males and females) from eating olestra snack foods was 5.9% (Cooper et al. 1997e). For the top 10% of snack eaters (all ages), the reduction was calculated to be 9.5%. These estimates are still exaggerated because it was assumed in the analysis that all snack foods eaten were snacks made with olestra, an unlikely situation.

Figure 4 illustrates the effect of eating pattern on -carotene absorption. This figure shows the effects of olestra on serum -carotene measured when 1 ) olestra snack foods and foods containing -carotene are eaten in real-life dietary patterns, the analysis discussed above, 2 ) when olestra was eaten every day with meals but carotenoids were eaten ad libitum (Koonsvitsky et al. 1997, Weststrate and van het Hof 1995), and 3 ) when carotenoids and olestra were always eaten together (Schlagheck et al. 1997b).

The likely effect of olestra on the availability of other carotenoids would be expected to be similar to, or less than that calculated for -carotene because -carotene is one of the most lipophilic carotenoids (Cooper et al. 1997e). Calculations similar to those discussed above were not made for other dietary components such as the fat-soluble vitamins. However, the effect of olestra on these nutrients in real life would be expected also to be considerably less than the effects measured in the pig and human studies because the foods containing these nutrients are only occasionally eaten together with snack foods.

The interaction of olestra with carotenoids and other dietary components is not different than many other interactions that occur between many other dietary components. For example, carotenoid absorption can be reduced by as much as 50% when carotenoids are eaten with large amounts of fiber (Rock and Swendseid 1992), and -carotene absorption is reduced by more than 70% from meals containing only small amounts of fat (Dimitrov et al. 1988). A normal serving of milk can reduce whole-body retention of iron from a standard breakfast by as much as 50% (Deehr et al. 1990), and drinking tea with a typical breakfast has been shown to reduce the absorption of iron from that meal by as much as 60% (Rossander et al. 1979). Although such effects might be significant at any one meal, because of variations in dietary components and eating patterns, they are generally not nutritionally significant over time.

The variation in carotenoid bioavailability for people eating olestra snacks is likely to be within the normal variation of dietary carotenoid bioavailability and likely not be nutritionally meaningful. Further, any effect of a decrease in carotenoid availability on vitamin A stores will be offset by the addition of vitamin A to the snack food. The FDA concluded, on the basis of the scientific evidence available, that the effects of olestra on carotenoid absorption is "reasonably certain" to be nutritionally insignificant and that there is currently no need or justification to add carotenoids to olestra snack foods (Federal Register 1996).

Because of the observed associations and hypothesis, the potential of olestra to affect the absorption of phytochemicals was assessed (Cooper et al. 1997e). As a first step in making the assessment, octanol-water partition coefficients (log₁₀ p_c) for those molecules shown to be affected, or not affected by olestra were compiled. Octanol-water partition coefficients provide a measure of the lipophilicity of a molecule (i.e., its equilibrium distribution between an aqueous phase and an oil phase). Comparison of log₁₀ p_c values of those molecules for which olestra does not affect absorption with those of molecules that are affected showed that olestra affects the absorption only of molecules with log₁₀ p_c values <7.5 (Cooper et al. 1997e). The effect of olestra on the absorption of molecules with log₁₀ p_c values in the 7.5-9 range is minimal. As a next step, log₁₀ p_c values for almost 400 phytochemicals, making up all of the major classes, were calculated. Only two classes contained molecules with log₁₀ p_c values > 7.5 and thus likely to be affected by olestra. These were the carotenoids and the phytosterols.

Carotenoids are only one of many phytochemicals found in fruits and vegetables, and it is unlikely that they are the only component responsible for the apparent beneficial effects of high fruit and vegetable intake. As discussed above, the effect of olestra on carotenoid absorption when olestra snack foods are eaten in real life is estimated to be <10%. A reduction in the absorption of one component by <10% is unlikely to affect the beneficial effects associated with diets rich in fruits and vegetables.

The other class of phytochemicals that contains molecules sufficiently lipophilic that their absorption might be affected by olestra is the phytosterols. Phytosterols, when taken in large amounts, can reduce cholesterol absorption (Linscheer and Vergrosen 1988). A small reduction in the absorption of these phytochemicals by olestra is unlikely to pose a risk because large intakes of olestra also have the potential to reduce cholesterol absorption (Jandacek et al. 1990). Further, the absorption of large amounts of phytosterols themselves is undesirable inasmuch as it may result in increased risk of hypercholesterolemia (Linscheer and Vergrosen 1988).

To ensure that the results from the pig and human studies can be used to assess the potential for olestra to affect the nutritional status of such subgroups, the nutrient needs and dietary patterns represented in the olestra studies were compared with those of potentially at-risk subgroups (Middleton et al. 1997). The first step was to identify subgroups potentially at-risk either because of unique dietary patterns or nutrient needs different than those of the test subjects. This was done by compiling requirements for and intakes of the nutrients selected for evaluation in the studies for subgroups of the population. Olestra intakes were estimated for the same subgroups. This analysis showed that children, teenager and young adults, women from low-income families and vegetarians had dietary patterns that produced olestra-to-nutrient intake ratios greater than those of adults. Subgroups identified with high nutrient requirements included children, teenagers, and pregnant or lactating women.

A comparison of nutrient needs and olestra-to-nutrient intake ratios of the identified subgroups with those covered in the studies showed that the nutrient needs of the rapidly growing pigs used in the studies were greater than those of any of the subgroups for any nutrient. Also, olestra-to-nutrient intake ratios fed in the studies were greater than the ratios calculated for any subgroup for all nutrients except calcium, a micronutrient not affected by olestra. Thus, the effects (or lack of effects) of olestra on fat-soluble and water-soluble nutrients observed in the studies are applicable to these subgroups and indicate that no subgroup of the population will be placed at nutritional risk from eating olestra snacks.

Detailed information on the nature of these GI symptoms was obtained in the two 8-wk studies in which subjects used questionnaires to identify each GI symptom they experienced, indicated the length of each episode of each symptom and graded the severity. Because the demographics of the subject populations in the two 8-wk studies, a total of 192 adults, 18-44 y of age, were essentially the same and the protocols were identical, it is appropriate to combine the GI symptom data from the two studies.

The average severity of the GI symptoms is shown in Figure 5 for all symptoms, abdominal cramping and diarrhea for those subjects reporting symptoms in both studies (1 = mild, 2 = moderate, 3 = severe). Abdominal cramping and diarrhea were broken out because they are the symptoms of most concern. Similarly, the percentage of possible symptom-days is shown in Figure 6 for the combined studies. A symptom-day is defined as a day in which one or more symptoms were experienced with more than usual frequency, as reported by the subjects. Symptom-days were used to characterize the symptoms because they were transient in nature, abating and recurring. The maximum possible number of symptom-days for a given test group is obtained for a given symptom by multiplying the number of subjects in the group by 56, the number of days in the study.

Generally, the symptoms were mild to moderate in severity, and the severity was not dose responsive with respect to olestra intake. There was only 1 wk in which the average diarrhea grade was severe and that was in the placebo group at wk 3. The percentage of symptom days was generally dose responsive with respect to olestra intake; however, the placebo and 8 g/d olestra groups reported GI symptoms, including diarrhea and cramping, to essentially the same extent. Subjects eating 8 g/d olestra, an amount more than twice the estimated mean chronic olestra intake (3.1 g/d, all ages, males and females) from savory snacks (Webb et al. 1997) reported no symptoms on 90% or more of the days on which they were eating olestra snacks.

Many of the GI symptoms reported during the olestra studies were related to changes in stool consistency. In view of its properties (e.g., lipophilic, nondigestible, nonabsorbed), it is not surprising that olestra affects stool consistency. Large amounts of a highly lipophilic substance in the bowel can disrupt the fecal matrix and produce soft or loose stools. In extreme cases, this can be perceived as diarrhea. This stool-softening phenomenon may be akin to the stool-softening effects observed with liquid petrolatum and oils such as olive oil (Curry 1986). In the pig studies, variations in fecal consistency were noted with larger numbers of pasty feces being associated with higher dietary concentrations of olestra (Cooper et al. 1997a, 1997b, 1997c and 1997d).

The GI symptoms did not affect protocol compliance or the integrity of the findings from the studies. In the two 8-wk studies, the subjects ate more than 90% of the meals; only six subjects (in either the 20 g/d olestra groups or the 32 g/d olestra groups) temporarily stopped eating olestra foods because of the GI symptoms, and one subject withdrew because of persistent heartburn (Schlagheck et al. 1997a and 1997b). In the 16-wk study, only four of the 219 subjects enrolled withdrew because of GI symptoms, and olestra consumption was 98% of the targeted 18 g/d amount (Koonsvitsky et al. 1997).

The diarrhea reported by the individuals eating olestra was not pathological diarrhea, but rather an extreme case of stool softening. Pathological diarrhea could lead to malabsorption and thus cause changes in the absorption of water-soluble nutrients. The absorption of water-soluble nutrients was not affected by olestra in the subjects who reported diarrhea (Schlagheck et al. 1997a and 1997b). Further, clinical chemistry, hematology and urinalysis data collected on subjects who reported diarrhea on the day of or the day before blood and urine samples were taken showed no evidence of significant fluid loss such as hemoconcentration or electrolyte imbalance. Finally, no diarrhea was observed in pigs fed olestra at dietary concentrations as high as 7.7% (Cooper et al. 1997a, 1997b, 1997c and 1997d).

The incidence of GI symptoms reported in these studies is greater than that likely to occur when olestra snacks are eaten in real life because olestra was present in the GI tract at all times in amounts that exceeded intakes estimated for savory snack consumption by severalfold. The nature and frequency of GI symptoms reported by people eating either snacks prepared with olestra or triglyceride under real-life conditions have been determined in several consumer tests. In one such test, female heads of households were allowed to choose potato chips prepared with either olestra or triglyceride, in an amount and at a frequency they desired, over a 5-mo period. In this test, more than 2,000 subjects ate chips prepared with olestra and more than 1,000 ate regular chips (Lawson et al. 1997). Of the subjects who ate either kind of chips, < 1% voluntarily reported GI symptoms and there were no significant differences between the groups in the reports of any of the symptoms except flatulence, which was increased for the group who ate the olestra chips.

GI symptoms that may be experienced by individuals eating olestra snacks present no health risks, a conclusion also reached by the FDA (Federal Register 1996). These symptoms are not different than the symptoms associated with the consumption of other dietary components such as fibers (Anderson and Akanji 1991) and food additives such as sorbitol (Corazza et al. 1988, Hyams 1983) and are not worse in individuals with diseased GI tracts. This is illustrated by the results of a study in patients with quiescent inflammatory bowel disease (Zorich et al. 1997). Patients given 20 g/d of olestra for 4 wk reported no more adverse events related to the GI tract than those given triglyceride, with one exception. An increase in the number of daily bowel movements on one or more days was reported by more patients in the olestra group than in the placebo group. An increase in the number of bowel movements is not unexpected for individuals eating large amounts of olestra because of the increased fecal bulk.

It is important for consumers to be aware of the potential for olestra to produce GI symptoms in order to preclude unnecessary concern, and perhaps inappropriate medical treatment. Therefore, olestra products will carry a label informing the consumer that certain GI effects may occur (Federal Register 1996).

Whenever any new ingredient is introduced into the food chain, postmarketing surveillance is prudent and commonly occurs. Such is the case with olestra. Procter & Gamble is carrying out a postmarketing surveillance program consisting of several components. The spontaneous reporting of alleged undesirable effects is being monitored via an 800 telephone number provided on the product label. Olestra exposure, both intake and frequency of consumption, is also being monitored. In addition, prospective observational epidemiologic studies are being conducted to determine the nature, severity, incidence and prevalence of any effects on nutritional status and any gastrointestinal effects among individuals who eat olestra snacks under free-living conditions.