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American Journal of Clinical Nutrition, Vol. 83, No. 3, 624-631, March 2006
© 2006 American Society for Nutrition

ORIGINAL RESEARCH COMMUNICATION

Olestra is associated with slight reductions in serum carotenoids but does not markedly influence serum fat-soluble vitamin concentrations1,2,4

Marian L Neuhouser, Cheryl L Rock, Alan R Kristal, Ruth E Patterson, Dianne Neumark-Sztainer, Lawrence J Cheskin and Mark D Thornquist

1 From the Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA (MLN, ARK, REP, and MDT); the Department of Family and Preventive Medicine, University of California, San Diego, CA (CLR); the School of Public Health and Community Medicine, University of Washington, Seattle, WA (ARK and MDT); the Division of Epidemiology, University of Minnesota, Minneapolis, MN (DN-S); and the Division of Gastroenterology, Johns Hopkins School of Medicine, Baltimore, MD (LJC)

2 Presented in part at Experimental Biology 2004, held in Washington, DC.

3 Supported by The Procter & Gamble Company (Cincinnati, OH).

4 Address reprint requests to ML Neuhouser, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, PO Box 19024, Seattle, WA 98109-1024. E-mail: mneuhous{at}fhcrc.org.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: The 1996 Food and Drug Administration approval of the fat substitute olestra (sucrose polyester) called for active postmarketing surveillance because preapproval studies showed that olestra may lower circulating concentrations of fat-soluble nutrients such as vitamins and carotenoids.

Objective: The objective of the Olestra Post-Marketing Surveillance Study was to examine whether customary consumption of olestra-containing savory snacks was associated with changes in serum fat-soluble vitamin and carotenoid concentrations among free-living persons in geographically and ethnically distinct US cities.

Design: Adults (n = 2535) and their children aged 12–17 y (n = 272) in Baltimore, Minneapolis, and San Diego attended clinic visits during which data were collected on diet, savory snack consumption, lifestyle, and anthropometric indexes. Blood samples were drawn to assay carotenoids and vitamins A, D, E, and K. Data and blood samples were collected both before and after the nationwide introduction of olestra. General estimating equations were used in multivariate-adjusted models that examined olestra’s association with the specified serum nutrients.

Results: Compared with no intake, the top 2 tertiles of olestra use in adults were associated with circulating carotenoid concentrations that were modestly but significantly lower (4.3% to 22.4%). There were no significant associations of olestra with any serum nutrients among adolescents.

Conclusions: This active postmarketing surveillance study of a food additive suggests that small decreases in serum fat-soluble nutrients are attributable to olestra use. Although health outcomes were not measured here, it is unlikely that these small changes in nutrient measures would adversely affect health.

Key Words: Olestra • sucrose polyester • carotenoids • vitamin A • vitamin E • vitamin D • vitamin K • postmarketing surveillance


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The Center for Food Safety and Applied Nutrition at the Food and Drug Administration (FDA; Internet: www.cfsan.fda.gov) oversees the approval, labeling, and regulation of food additives and other food ingredients in the United States. To obtain FDA approval for a new food additive, manufacturers must submit a food additive petition that includes information on the identity and composition of the ingredient, the proposed use of the ingredient in food, the estimated amounts to be added to foods, and data on human safety (1). A particularly scrutinized food additive petition was for the fat substitute olestra (Procter & Gamble, Cincinnati, OH). In 1996 the FDA approved the use of this new fat substitute as an ingredient in the manufacture of savory snacks such as potato chips, corn chips, extruded snacks, and crackers.

Olestra (sucrose polyester) is a nonabsorbable, noncaloric fat substitute that has the organoleptic properties of fat and is stable at temperatures used for baking and frying (2). Because olestra is neither hydrolyzed by gastrointestinal enzymes nor absorbed, however, it has the capability to interfere with the absorption of fat-soluble nutrients. Animal model and human experimental studies published before the FDA’s approval of olestra consistently showed that olestra could sequester carotenoids and fat-soluble vitamins (2–5). For these reasons, FDA approval required that all olestra-containing products include the addition of vitamins A, D, E, and K and a label statement indicating that the extra vitamins were intended to compensate for any olestra-induced nutritional losses (6, 7). The FDA did not require the addition of carotenoids to olestra products because these plant compounds are not known to be required for human nutrition (8).

Most manufactured foods are subject to passive surveillance, in which the manufacturer collects consumer-initiated comments or complaints about a food either through a toll-free telephone number or a website address provided on the food packaging. As an additional element of olestra approval, however, the FDA requested the establishment of an active postmarketing surveillance study (6). Active surveillance rigorously examines the association of an exposure on a prespecified health or health-related outcome. Olestra was the first food ingredient to be subject to active postmarketing surveillance in the United States.

The Olestra Post-Marketing Surveillance Study was conducted by scientists at the Fred Hutchinson Cancer Research Center (Coordinating Center), the Johns Hopkins University, the University of Minnesota, and the University of California, San Diego. Funding was provided by the Procter & Gamble Company per the directive of the FDA, but by contractual agreements the scientists at the coordinating center and the university-based field sites were solely and independently responsible for study design; data collection, management, and analysis; and publications. Preliminary results were presented to the FDA’s Food Advisory Council in 1998 (9). Here we present the final results of the study.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study design
The principal aim of the Olestra Post-Marketing Surveillance Study was to assess olestra consumption and its association with serum concentrations of fat-soluble vitamins and carotenoids among US consumers. Specifically, we tested the hypothesis that olestra-associated changes in serum concentrations of fat-soluble vitamins and carotenoids would be <10% on the basis of the assumption that changes below this cutoff are consistent with random variation.

To test the study hypothesis, 3 phases of the Surveillance Study were conducted in a parallel manner. The first study phase was a list-assisted random-digit-dial telephone survey conducted by Westat Inc (Rockville, MD) in which adults 18 y of age and older in 4 US cities (Indianapolis, Baltimore, Minneapolis, and San Diego) and their surrounding suburbs and unincorporated areas were recruited to complete a telephone survey with a focus on beliefs and attitudes about diet and health; usual fruit, vegetable, and savory snack consumption; and demographic characteristics. During the second study phase, a random sample of the telephone survey respondents was invited to join a clinical component of the study in which they completed detailed questionnaires on diet, medical history, and lifestyle habits; provided blood samples and anthropometric measures; and completed quarterly follow-up telephone calls over a 1-y period. These clinic visits were conducted between October 1997 and April 1998, before the introduction of olestra-containing products in the US marketplace. Telephone-based interviews and clinic visits resumed in October of 1998 (after olestra became available) and were conducted continuously, as new independent samples, until April 2000 to obtain data both before and after the availability of olestra-containing foods in the marketplace. For the third and final study phase, a subset of participants who were part of the first clinic cross-section in 1997–1998 were invited to continue in the study for an additional 2 y of data collection during which all measures were repeated. Thus, the overall design consisted of a population-based telephone survey, independent waves of cross-sectional clinic visits, and cohort clinic visits. Further details about the study design and baseline results were published previously (9–12).

Children and adolescents were recruited for study participation in the following manner. If the household recruited to complete the clinic visit contained a child aged 7–17 y, then the child was invited to join the study. In households with more than one child, the child with a birthday closest to the date of the phone call was selected as the participant. For this report, we included only adolescents aged 12–17 y because they completed the same measures as the adults, whereas younger participants completed different questionnaires and assessment tools. Adolescents attended the visits with their parents or guardians, but all study-related interviews and data collection were conducted privately. Both adolescents and adults with medical conditions that would interfere with accurate measurements of the serum analytes under investigation (eg, cystic fibrosis, kidney disease requiring dialysis, or short bowel syndrome) were excluded (8, 13). We also excluded participants who reported pregnancy on the day of the clinic visit because the expanded plasma volume of pregnancy complicates the interpretation of serum nutrient concentrations (14).

The study participants were not aware that they were in a study examining the effects of olestra-containing snack foods, and the study was operationalized as the National Study of Nutrition and Health. This blinding was considered the optimal way to conduct an unbiased surveillance study to assess population-level olestra consumption and its association with serum fat-soluble nutrients in free-living persons for the following reason. Randomized controlled trials in both humans and animals were conducted before the FDA approval of olestra to investigate general safety, dose-response effects, and adverse events (2, 4, 5, 15), but these experimental studies were not designed to answer questions about who would adopt foods made with a macronutrient substitute or olestra’s effect on nutritional status when consumed in a manner consistent with the customary snack habits of free-living persons. The Institutional Review Boards of the Fred Hutchinson Cancer Research Center, Johns Hopkins University, the University of Minnesota, and the University of California, San Diego, approved all study procedures. Written informed consent was obtained from all participants. Because the Indianapolis clinic was considered the test site and used different study instruments, those results are not included in this report and were previously reported (9).

Measures
Dietary assessment
Nutrient intake was assessed with a validated 122-item food-frequency questionnaire (FFQ) (16) plus a 16-item savory snack questionnaire that was created expressly for this study (17). The snack-food questionnaire included questions on use of regular, reduced-fat, baked, nonfat, and fat substitute (ie, olestra) potato chips, tortilla chips, pretzels, extruded snacks, and crackers (17). The FFQ and the snack-food questionnaire both queried about usual consumption frequency and portion sizes during the previous month. The nutrient database for these questionnaires was derived from the University of Minnesota’s Nutrition Coordinating Center (NCC) Nutrient Database and included the 1999 US Department of Agriculture–NCC Carotenoid Database for US foods (18). Our approach to analyzing the FFQs and the algorithms for analysis are published elsewhere (19, 20). FFQs with energy intakes <800 kcal/d or >5000 kcal/d for men (n = 100) and <600 kcal/d or >4000 kcal/d for women (n = 144) were excluded because they were considered to be unreliable (21).

Data on vitamin supplement use over the past month were obtained from all participants by using a validated inventory procedure (22, 23) that was modified to collect detailed dosage information on the nutrients of interest to this study: vitamins A, D, E, and K and ß-carotene (the only carotenoid widely available in supplement formulations at the time). Total micronutrient intake used in analyses included sources from all supplements plus food.

Blood collection and processing
Phlebotomists collected blood samples by venipuncture into serum-separating tubes, which were protected from heat and light throughout handling and processing. Adults were semifasting (≥6 h) at the time of blood collection, and adolescents were nonfasting. All serum was stored locally at each clinic site at –20°C for no longer than 4 d, was shipped to the study’s Coordinating Center on dry ice, and was stored at –70°C until analyzed.

Laboratory analyses
Quintiles Laboratories (Atlanta, GA) performed the analyses of serum vitamin E ({alpha}-tocopherol), vitamin A (all-trans-retinol), vitamin D (25-hydroxyvitamin D), 6 carotenoids ({alpha}-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein, and zeaxanthin), and total cholesterol and triacylglycerols (used as adjustment factors). The serum carotenoids, tocopherols, and retinol were assayed by using reversed-phase HPLC. The CVs for individual analytes ranged from 1.9% to 9.8%. 25-Hydroxyvitamin D was assayed by using the INCSTAR 125I radioimmunoassay kit (Stillwater, MN). The interassay CV for serum vitamin D ranged between 5.7% and 9.2%. Total serum cholesterol and triacylglycerols were analyzed by using enzymatic methods. Precision was evaluated by using packaged reagents and pooled human serum and control serum samples; both interassay precision and bias were <3%. The Vitamin K Laboratory at the US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University conducted the analyses of serum vitamin K (phylloquinone) by using HPLC with vitamin K1(25) as an internal standard per the method of Davidson and Sadowski (24). One low-normal and one high-normal concentration quality-control sample were analyzed with each batch of samples with between-day variability of 9.7% and 5.3%, respectively. Laboratory personal were blinded to all personal characteristics of the study participants and had no knowledge of whether the samples were from participants who did or did not consume olestra.

Anthropometry
Trained staff used a common protocol at all 3 clinic sites to measure height and weight at each clinic visit. Body mass index (BMI) was calculated at weight (kg)/height (m2). Participants were classified as being normal weight (BMI = 18.5–24.9), overweight (BMI = 25.0–29.9), or obese (BMI ≥ 30.0) according to the Expert Panel on the Identification, Evaluation and Treatment of Overweight and Obesity in Adults (25). Although that report defined overweight and obesity for adults, we used the same cutoffs for adolescents to be consistent across the analyses.

Other measures
The frequency and intensity of both occupational and leisure-time physical activity were measured with the use of standard questionnaires (26). To estimate the intensity of physical activity in metabolic equivalents (METs), the number of reported minutes per week spent in activity or exercise was multiplied by an estimate of METs per exercise session (26). Staff members also collected information on medical history, usual sun exposure, household income, and alcohol and tobacco use. Demographic characteristics were collected during the initial study recruitment telephone call for the adults and during the clinic visit for the adolescents.

Statistical analyses
Descriptive statistics were used to characterize the study sample. We examined the distributions of all continuous variables, including the outcome variables, and those that did not fit a normal distribution were transformed by the natural logarithm. We hypothesized at the start of the surveillance study that changes in serum concentrations of fat-soluble vitamins and carotenoids attributable to olestra consumption would be <10% (a level consistent with random variation), and we projected that that we would have 80% power to detect these differences between persons who did and did not consume olestra (9). Statistical significance was set at P < 0.05. We used the general estimating equation (GEE) modification of linear regression as our analytic approach to test the study hypotheses. This method allowed us to simultaneously examine the cross-sectional and cohort relations between the independent variables and the serum nutrients of interest and permitted us to account for within-person variation over time (27). Our models used an autoregressive correlation structure, which is a common approach for the analysis of longitudinal data. The maximum number of observations from any one participant was 3, whereas the most common number of observations was 2.

Olestra consumption, the primary exposure, was categorized into tertiles among those who reported olestra consumption on the snack FFQ; the quartile categories used in the multivariate models were no consumption, <1.3 g/wk, 1.3–4.4 g/wk, and >4.4 g/wk for the adults, and no consumption, <1.25 g/wk, 1.25–4.8 g/wk, and >4.8 g/wk for the adolescents. Each 1-oz serving (28 g) of savory snacks made with olestra contains {approx}8 g olestra. The results in the tables of associations of olestra intake with serum vitamin and carotenoid concentrations were generated from the empirical SE parameter estimates from the GEE models; these estimates were robust with respect to the structure of the working correlation matrix. All models included age, sex, race/ethnicity, energy intake, the dietary intake of the serum nutrient being modeled (food + supplements), clinic site, year of blood sample collection, and an indicator variable for study participant status (cross-sectional or cohort member). Models for serum {alpha}-tocopherol and carotenoids included serum cholesterol, the model for serum vitamin K included serum triacylglycerol, and the model for vitamin D included sunlight exposure. Additional variables, including percentage of energy from fat, daily servings of fruit and vegetables, BMI, physical activity, smoking, and alcohol use were allowed in the model if the P value for their parameter estimate was <0.10. The selection of these variables was based on our prior reports focused on determinants of serum concentrations of fat-soluble vitamins and carotenoids in this population (11, 12).

For the analyses in the present report, we first constructed the base model for each outcome or serum nutrient concentration. Inclusion of other covariates was based on the P value of the score statistic for type III contrasts for each effect, and, as noted above, covariates were retained in the model if the P value was <0.10. Finally, olestra was added to each model to assess its association with each serum nutrient concentration. The ß coefficient for each of the 3 olestra consumption group variables is interpreted as the multivariate-adjusted percentage change in the respective serum nutrient relative to no olestra consumption, after appropriate back transformation of the log-transformed outcome variables. The models were adjusted for multiple comparisons by using the Bonferroni adjustment where appropriate. All statistical tests were two-sided, and analyses were performed with SAS (version 8.2; SAS Institute Inc, Cary, NC).

Among the adults, 3975 observations were available for analysis (2704 from the cohort and 1271 from the cross-sectional visits). Of these, 247 were removed because of energy intake outliers from the FFQ (n = 205), missing serum data (n = 11), or a current pregnancy at the time of the blood sample collection (n = 31), leaving 3728 observations from 2535 individuals for analysis. Among the adolescents, there were 392 observations (266 cohort and 126 cross-sectional). Forty observations were removed because of energy intake outliers from the FFQ (n = 39) and a reported pregnancy at the clinic visit (n = 1). Thus, 352 adolescent observations were retained (241 cohort and 111 cross-sectional) from 272 individuals.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Demographic and health-related characteristics of the study population are described in Table 1Go. Overall, the study sample was well-educated, and among the adults, predominantly female. About 65% of the adults and 37% of the adolescents were overweight or obese. Notably, 24.6% of the adults and 38.5% of the adolescents in this report represented minority populations. In general, users of olestra tended to be nonwhite with at least some college education. The mean daily olestra consumption among both adults and adolescents was {approx}0.75 g/d, and those in the top decile consumed about 2 full servings per week, which suggests that use was very occasional at the population level (data not shown).


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  		TABLE 1. Demographic and health-related characteristics of participants in the Olestra Post-Marketing Surveillance Study

 
Distributions of the serum nutrient concentrations are presented in Table 2Go. There were no remarkable outliers in these distributions.


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  		TABLE 2. Serum fat-soluble vitamin and carotenoid concentrations in adults and adolescents in the Olestra Post-Marketing Surveillance Study1

 
The associations of olestra with serum nutrient concentrations are presented in Tables 3Go-6Go. At the top of each of these tables, we present the multivariate-adjusted mean (±SE) serum nutrient concentrations without consideration of the olestra effect. This is followed by the percentage change in serum concentrations due to olestra intake. Olestra intake is presented as tertiles, and each percentage change is to be compared with "no intake."


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  		TABLE 3. Associations of olestra intake with serum fat-soluble vitamin concentrations in free-living adults1

 

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  		TABLE 6. Associations of olestra intake with serum carotenoid concentrations in free-living adolescents aged 12–17 y1

 
There were no significant associations of olestra use with fat-soluble vitamin concentrations (Table 3Go). However, there were fairly consistent reductions in serum carotenoid concentrations associated with increasing olestra intake (Table 4Go). Statistically significant trends were noted for all carotenoids except serum lutein + zeaxanthin. The largest percentage reduction was noted for {alpha}-carotene. Compared with no olestra intake, there were 22% and 14% reductions in serum {alpha}-carotene concentrations for the middle and top tertiles of consumption, respectively. Compared with no olestra intake, there was a 10% reduction in serum ß-carotene, a 6.5% reduction in serum ß-cryptoxanthin, and a nearly 12% reduction in serum lycopene concentration. For total carotenoids, there was a 9.7% reduction in serum carotenoids for the top tertile of olestra consumption compared with no olestra consumption.


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  		TABLE 4. Associations of olestra intake with serum carotenoid concentrations in free-living adults1

 
In adolescents, there was no evidence for associations of olestra intake with serum concentrations of fat-soluble vitamins (Table 5Go) and modest, but not significant, reductions in serum carotenoid concentrations (Table 6Go). As in adults, the largest reductions attributable to olestra intake were in serum concentrations of {alpha}-carotene and ß-carotene. However, there were no clear patterns of associations; neither the parameter estimates nor the tests for linear trend were statistically significant.


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  		TABLE 5. Associations of olestra intake with serum fat-soluble vitamin concentrations in free-living adolescents aged 12–17 y1

 
We conducted additional analyses to test the olestra responses among various subgroups, such as those participants who were overweight or obese. Although BMI was strongly, inversely correlated with all serum nutrient outcome measures, there was no differential association of olestra intake with serum nutrient measures between those who were obese and those of normal weight (data not shown). Thus, although many of the covariates presented in the models were confounders, there was no effect modification between characteristics such as obesity or dietary supplement use with olestra in relation to serum nutrient concentrations.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The present report describes findings from the first FDA-sanctioned postmarketing surveillance study of a food additive in the United States. The principal findings were that modest consumption of savory snacks made with the fat substitute olestra is associated with small and mostly statistically nonsignificant associations with serum concentrations of fat-soluble vitamins and carotenoids among healthy free-living adults. The magnitudes of association ranged from a multivariate-adjusted 1.6% increase to an 8.7% decrease in serum fat-soluble vitamin concentrations for the top tertile of olestra consumption compared with no consumption. The single statistically significant finding was a 3.2% reduction in serum vitamin E in the highest tertile of olestra consumption relative to no consumption. Among adolescents, the associations of olestra with serum fat-soluble vitamin concentrations were neither statistically significant nor related in a dose-response fashion to olestra intake. For serum carotenoids, however, among the adults, compared with no olestra intake, the top tertile of olestra consumption was associated with statistically significant reductions in serum {alpha}-carotene (14.1%), ß-carotene (10.1%), and lycopene (11.8%). It is important to reiterate that the principal aims of this surveillance study were related to measures of circulating fat-soluble nutrients; this study was not designed to measure health outcomes, either those directly associated with olestra consumption or those indirectly associated through changes in serum nutrient concentrations.

Several important questions about the safety of olestra can be addressed with the data presented in this report. First, the addition of vitamins A, D, E, and K to olestra-containing savory snacks appears to offset any potential vitamin losses, because there were no clinically meaningful reductions in fat-soluble vitamin concentrations attributable to olestra consumption. Although there was a statistically significant 3.2% decrease in serum vitamin E concentrations for the top tertile of olestra consumption compared with no consumption among adults, there were no deficient values; the bottom 1% of the serum vitamin E distribution was 13.5 µmol/L for adults and 10.9 µmol/L for adolescents (data not shown).

Second, although the olestra-induced percentage changes in serum carotenoid concentrations were modest but statistically significant, the absolute changes were very small. For example, compared with study participants who consumed no olestra, participants who consumed >4.4 g olestra/wk had 14.4% (P < 0.05) lower serum {alpha}-carotene concentrations, or a change from 0.07 to 0.06 µmol/L. Notably, the median of the serum {alpha}-carotene distribution for adults in the third National Health and Nutrition Examination Survey was 0.07 µmol/L (8), which suggests that even for participants whose circulating concentrations of {alpha}-carotene decreased because of olestra intake, overall concentrations were still within the midrange of US adults. The other serum carotenoids in the Surveillance Study followed a similar pattern.

A few studies published since the 1996 FDA approval of olestra have examined associations with serum carotenoids, and the results of those studies differ slightly from those in the present report. Kelly et al (28) reported a significant reduction in serum carotenoids after a 3-mo intervention period during which participants consumed a mean of 26.8 g olestra/d (equivalent to {approx}3 servings daily). A Netherlands intervention study randomly assigned subjects to various olestra consumption levels (0, 7, 10, or 17 g/d) and reported significant decreases in serum carotenoids after 1 y for all levels of consumption (29). It is important to note, however, that these 2 studies were interventions that tested defined amounts of consumption, which may or may not reflect usual snack habits. We are unaware of other studies that have assessed associations of olestra consumption resembling customary snacking habits of free-living persons with circulating concentrations of serum fat-soluble vitamins or carotenoids.

These observations about olestra play an important part in the overall evaluation of the fat substitute’s role in the food supply. Consumer groups and some members of the scientific community have criticized the FDA’s approval of olestra (30, 31). Yet, there appear to be benefits of this zero-calorie fat substitute. Several well-controlled intervention studies that tested the effect of olestra consumption on energy balance have been published since the 1996 FDA approval of olestra (28, 32–35). Specifically, substitution of olestra in a reduced-fat diet results in significant and sustained weight loss and improved lipid profiles compared with a low-fat diet alone (32, 34, 35). These results are consistent with data we previously published from the first phase of the Olestra Post-Marketing Surveillance Study showing that olestra consumption was associated with statistically significant reductions in weight and total serum cholesterol (36). In addition, although the Surveillance Study was not designed to measure specific health outcomes, we note that the Netherlands intervention study showed that at higher daily consumption of olestra, which resulted in greater percentage changes in serum carotenoid concentrations than in our study, there was no association of serum nutrient changes with markers of disease risk, such as macular pigment density and flow-mediated vasodilation of the brachial artery (29). Finally, published reports have been unable to show significant associations of olestra intake with gastrointestinal symptoms (37, 38). Although we make no clinical recommendation about the use or avoidance of olestra, the preponderance of peer-reviewed published evidence suggests no harm and potential benefit from the fat substitute olestra. Given the US obesity epidemic and its myriad of health concerns (39), clinicians and scientists will need to ask whether the benefits of a food ingredient that may assist with weight management and improved serum lipid profiles outweighs small changes in serum fat-soluble nutrient concentrations.

Our study had several strengths. First, our approach to testing whether olestra consumption interfered with fat-soluble nutrient concentrations in the US population used a design in which study participants were recruited from 3 distinct geographic regions with a range of demographic and lifestyle characteristics. Furthermore, the study used standardized data collection instruments and central research laboratories with strict quality control for all assays. Second, the use of repeated measures of dietary assessment and blood nutrient concentrations improved the precision of our results (40). Third, because the study participants were not aware that they were in a surveillance study to monitor olestra consumption, we assume that there was no underlying incentive to differentially over- or underreport olestra consumption.

Some limitations of our study should also be mentioned. Although our multivariate models included variables known to influence serum fat-soluble vitamin and carotenoid concentrations, potential confounding variables may exist that we either did not measure or measured with insufficient precision, which would result in uncontrolled confounding or the possibility that our findings were by chance alone. Furthermore, we acknowledge that customary olestra consumption among free-living persons was lower than expected and certainly lower than the amounts offered in clinical trials. Of the observations in the Olestra Post-Marketing Surveillance Study, which included habitual users of savory snacks, 21.4% were associated with olestra consumption, but the top tertiles of consumption were 4.4 and 4.8 g/wk among the adults and adolescents, respectively. These levels of consumption represent about one-half of a serving per week. Pre-FDA approval studies estimated that mean daily intake would be {approx}4.4 g for persons aged 13–17 y, 3.7 g for adults aged 18–44 y, and 2.5 g for those aged 45–64 y (41). The lower than expected consumption in the surveillance study could be real, but it is also possible that consumption was underreported, which is common in observational studies (21, 42, 43).

In conclusion, the results of this first active postmarketing surveillance study of a food additive suggest that olestra consumption from savory snacks had no meaningful clinical association with serum fat-soluble vitamin concentrations but an association with small reductions in serum carotenoid concentrations. The study design used here may be useful for testing the association of other new foods or food ingredients entering the marketplace with health outcomes in free-living populations. Our findings support the 2003 FDA ruling that olestra-containing savory snacks would no longer be required to include a label statement informing consumers that olestra may interfere with the absorption of fat-soluble nutrients such as vitamins and carotenoids nor that vitamins A, D, E, and K have been added to the products. These vitamins remain in the ingredient listing but are classified as "dietarily insignificant" (44).


   ACKNOWLEDGMENTS
 
We express our gratitude to the study staff and volunteers who made this investigation possible. We also express thanks to John Peters, Dale Cooper, and Alison Eldridge for assistance in conducting this study and to Steven Schaffer for assistance with data management and analysis. We thank Westat Inc, Quintiles Laboratories, and the Vitamin K Laboratory at the USDA Human Nutrition Research Center on Aging at Tufts University for their technical expertise.

All authors contributed to the design and data collection of this study. MLN was responsible for writing and revising the manuscript and the other authors contributed significant advice during the laboratory and data analysis and manuscript revisions. None of the authors had personal or financial conflicts of interest.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Trissler RJ. From aspartame to Xenical. A look at the FDA review process. J Am Diet Assoc 1999;99:797–8.[Medline]
  2. Peters JC, Lawson KD, Middleton SJ, Triebwasser KC. Assessment of the nutritional effects of olestra, a nonabsorbed fat replacement: summary. J Nutr 1997;127:1719S–28S.
  3. Weststrate JA, van het Hof KH. Sucrose polyester and plasma carotenoid concentrations in healthy subjects. Am J Clin Nutr 1995;62:591–7.[Abstract/Free Full Text]
  4. Cooper DA, Berry DA, Jones MB, Kiorpes AL, Peters JC. Olestra’s effect on the status of vitamins A, D and E in the pig can be offset by increasing dietary levels of these vitamins. J Nutr 1997;127:1589S–608S.
  5. Cooper DA, Berry DA, Spendel VA, Kiorpes AL, Peters JC. The domestic pig as a model for evaluating olestra’s nutritional effects. J Nutr 1997;127:1555S–65S.
  6. US Department of Health and Human Services, Food and Drug Administration. 21 CFR part 172. Food additives permitted for direct addition to food for human consumption: olestra; final rule. Fed Regist 1996;62:3118–73.
  7. Prince DM, Welschenbach MA. Olestra: a new food additive. J Am Diet Assoc 1998;98:565–9.[Medline]
  8. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for vitamin C, vitamin E, selenium and carotenoids: a report of the Panel on Dietary Antioxidants and Related Compounds. Washington, DC: National Academy Press, 2000.
  9. Thornquist MD, Kristal AR, Patterson RE, et al. Olestra consumption does not predict serum concentrations of carotenoids and fat-soluble vitamins in free-living humans: early results from the sentinel site of the Olestra Post-Marketing Surveillance Study. J Nutr 2000;130:1711–8.[Abstract/Free Full Text]
  10. Kristal AR, Patterson RE, Neuhouser M, et al. Olestra Postmarketing Surveillance Study: design and baseline results from the sentinel site. J Am Diet Assoc 1998;98:1290–6.[Medline]
  11. Rock CL, Thornquist M, Kristal AR, et al. Demographic, dietary and lifestyle factors differentially explain variability in serum carotenoids and fat-soluble vitamins: baseline results from the Olestra Post-Marketing Surveillance Study. J Nutr 1999;129:855–64.[Abstract/Free Full Text]
  12. Neuhouser ML, Rock CL, Eldridge AL, et al. Serum concentrations of retinol, {alpha}-tocopherol and the carotenoids are influenced by diet, race and obesity in a sample of healthy adolescents. J Nutr 2001;131:2184–91.[Abstract/Free Full Text]
  13. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press, 2001.
  14. Lockitch G. Clinical biochemistry of pregnancy. Crit Rev Clin Lab Sci 1997;34:67–139.[Medline]
  15. Schlagheck TG, Kesler JM, Jones MB, et al. Olestra’s effect on vitamins D and E in humans can be offset by increasing dietary levels of these vitamins. J Nutr 1997;127:1666S–85S.
  16. Patterson RE, Kristal AR, Carter RA, Fels-Tinker L, Bolton MP, Agurs-Collins T. Measurement characteristics of the Women’s Health Initiative food frequency questionnaire. Ann Epidemiol 1999;9:178–87.[Medline]
  17. Neuhouser ML, Patterson RE, Kristal AR, Rock CL, Neumark-Sztainer D, Thornquist LJ. Do consumers of savory snacks have poor quality diets? J Am Diet Assoc 2000;100:576–9.[Medline]
  18. Holden JM, Eldridge AL, Beecher GR, et al. Carotenoid content of U.S. foods: an update of the database. J Food Comp Anal 1999;12:169–96.
  19. Kristal AR, Shattuck AL, Williams AE. Food frequency questionnaires for diet intervention research. Proceeding of the 17th National Nutrient Databank Conference, Baltimore, MD, 1992. Washington, DC: International Life Sciences Institute, 1992.
  20. Schakel SF, Buzzard IM, Gebhardt SE. Procedures for estimating nutrient values for food composition databases. J Food Comp Anal 1997;10:102–14.
  21. Willett W. Nutritional Epidemiology. 2nd ed. New York, NY: Oxford University Press, 1998.
  22. Patterson RE, Kristal AR, Levy L, McLerran D, White E. Validity of methods used to assess vitamin and mineral supplement use. Am J Epidemiol 1998;148:643–9.[Abstract/Free Full Text]
  23. Patterson RE, Levy L, Tinker LF, Kristal AR. Evaluation of a simplified vitamin supplement inventory developed for the Women’s Health Initiative. Public Health Nutr 1999;2:273–6.[Medline]
  24. Davidson KW, Sadowski JA. Determination of vitamin K compounds in plasma or serum by high performance liquid chromatography (HPLC) using post-column chemical reduction and fluorimetric detection. Methods Enzymol 1997;282:408–21.[Medline]
  25. Expert Panel on the Identification, Evaluation and Treatment of Overweight in Adults. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. Am J Clin Nutr 1998;68:899–917.[Medline]
  26. Ainsworth B, Haskell W, Whitt M. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 2000;32(suppl):S498–504.[Medline]
  27. Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika 1986;73:13–22.[Abstract/Free Full Text]
  28. Kelly SM, Shorthouse M, Cotterell JCR, et al. A 3-month, double-blind, controlled trial of feeding with sucrose polyester in human volunteers. Br J Nutr 1998;80:41–9.[Medline]
  29. Broekmans WMR, Klöpping-Ketelaars IAA, Weststrate JA, et al. Decreased carotenoid concentrations due to dietary sucrose polyesters do not affect possible markers of disease risk in humans. J Nutr 2003;133:720–6.[Abstract/Free Full Text]
  30. Jacobson M. Olestra snacks compared with regular snacks. Ann Intern Med 1999;131:866.[Free Full Text]
  31. Nestle M. The selling of olestra. Public Health Rep 1998;113:508–19.[Medline]
  32. Hill JO, Seagle HM, Johnson SL, et al. Effects of 14 d of covert substitution of olestra for conventional fat on spontaneous food intake. Am J Clin Nutr 1998;67:1178–85.[Abstract]
  33. Bray GA, Lovejoy JC, Most-Windhauser M, et al. A 9-mo randomized clinical trial comparing fat-substituted and fat-reduced diets in healthy obese men: Ole Study. Am J Clin Nutr 2002;76:928–34.[Abstract/Free Full Text]
  34. Lovejoy JC, Bray GA, Lefevre M, et al. Consumption of a controlled low-fat diet containing olestra for 9 months improves health risk factors in conjunction with weight loss in obese men: the Ole Study. Int J Obes Relat Metab Disord 2003;27:1242–9.[Medline]
  35. Roy HJ, Most MM, Sparti A, et al. Effect on body weight of replacing dietary fat with olestra for two or ten weeks in healthy men and women. J Am Coll Nutr 2002;21:259–67.[Abstract/Free Full Text]
  36. Patterson RE, Kristal AR, Peters JC, et al. Changes in diet, weight, and serum lipid levels associated with olestra consumption. Arch Intern Med 2000;160:2600–4.[Abstract/Free Full Text]
  37. McRorie J, Zorich NL, Riccardi K, et al. Effects of olestra and sorbitol consumption on objective measures of diarrhea: impact of stool viscosity on common gastrointestinal symptoms. Regul Toxicol Pharmacol 2000;31:59–67.[Medline]
  38. Sandler RS, Zorich NL, Filloon TG, et al. Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial. Ann Intern Med 1999;130:253–61.[Abstract/Free Full Text]
  39. Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999–2000. JAMA 2002;288:1723–7.[Abstract/Free Full Text]
  40. White E, Hunt JR, Casso D. Exposure measurement in cohort studies: the challenges of prospective data collection. Epidemiol Rev 1998;20:43–56.[Free Full Text]
  41. Webb DR, Harrison GG, Lee M-J, Huang M-H. Estimated consumption and eating frequency of olestra from savory snacks using menu census data. J Nutr 1997;127:1547S–54S.
  42. Subar A, Kipnis V, Troiano RP, et al. Using intake biomarkers to evaluate the extent of dietary misreporting in a large sample of adults: the OPEN Study. Am J Epidemiol 2003;158:1–13.[Abstract/Free Full Text]
  43. Prentice RL. Measurement error and results from analytic epidemiology dietary fat and breast cancer. J Natl Cancer Inst 1996;88:1738–47.[Abstract/Free Full Text]
  44. US Department of Health and Human Services, Food and Drug Administration. Food additives permitted for direct addition to food for human consumption; olestra; final rules. Fed Regist 2003;68:46363–402.
Received for publication May 31, 2005. Accepted for publication December 5, 2005.





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