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A randomized, double-blind study of the effect of olestra on disease activity in patients with quiescent inflammatory bowel disease. Olestra in IBD Study Group.

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.

Abdominal Pain↗

Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial.

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.

Abdominal Pain↗

Correlates of maintenance of a low-fat diet among women in the Women's Health Trial.

BACKGROUND: The Women's Health Trial (WHT) was a feasibility study for a randomized controlled trial designed to test the hypothesis that a reduction in dietary fat reduces breast cancer incidence among women age 45 to 69. Between 1984 and 1988, 2,064 women participated in its two phases. METHODS: A follow-up study of 525 women who were randomized to receive the WHT dietary intervention program was conducted to assess maintenance of the diet 1 year on average after the trial ended. Among 448 participants, the mean percentage of energy from fat as measured by a food frequency questionnaire was 40.0% at baseline, 26.3% at the end of the trial, and 27.7% at follow-up. Based on 408 women with complete data, a recursive model was estimated, describing the influence of baseline characteristics of the women on attendance at intervention program sessions, adherence to the diet during the trial, and long-term maintenance of the diet after the trial ended. The effects of women's experiences during the trial on adherence and long-term maintenance were investigated as well. RESULTS: Attendance at the educational sessions was strongly related to adherence to the diet during the trial (P less than 0.001), and adherence was the most important predictor of long-term maintenance (P less than 0.001). The percentage of energy from dietary fat at baseline was an important correlate of both adherence (P less than 0.001) and long-term maintenance (P less than 0.001). College-educated women were more likely to adhere to the diet during the trial (P less than 0.001). Feelings of deprivation adversely affected long-term maintenance (P less than 0.01), primarily through their effect on adherence during the trial (P = 0.01). Costliness of the diet in time and money negatively influenced long-term maintenance (P less than 0.05). Development of a distaste for fat encouraged adherence (P = 0.06). CONCLUSIONS: The low-fat dietary pattern established during the WHT was maintained for as long as 20 months after the trial ended. A recursive model was useful in analyzing the process and correlates of long-term maintenance of dietary behavior change. Both predisposing variables and women's experiences while on a low-fat diet were associated with long-term maintenance. The results suggest that feelings of deprivation should be avoided, perhaps by use of low-fat substitutes, by those attempting to lower their dietary fat and that more research is needed on the development of a distaste for fat among individuals who adopt low-fat diets.

Aged↗

Influence of medium-chain and long-chain triacylglycerols on the control of food intake in men.

Hunger may be delayed and food intake reduced under metabolic conditions that spare carbohydrate oxidation, especially during oxidation of medium-chain triacylglycerols (MCTs) or monounsaturated triacylglycerols. In 12 healthy, adult, male volunteers isolated and deprived of any time cues, we compared the effects of 4 high-carbohydrate breakfasts (1670 kJ) supplemented either with a fat substitute (Sub; 70 kJ) or with 1460 kJ fat as monounsaturated long-chain triacylglycerols (LCT-U), saturated long-chain triacylglycerols (LCT-S), or MCTs. In the first session we investigated the effects of these breakfasts on the following food intake variables: hunger ratings at repeated intervals, the time until the spontaneous request for the next 2 free-choice meals, and the amount of food consumed. In a second session with fixed lunches, we studied the effects of the same breakfasts on plasma glucose, insulin, triacylglycerol, fatty acid, and beta-hydroxybutyrate concentrations. The addition of any of the fats to the high-carbohydrate breakfasts did not alter hunger ratings, but significantly delayed the request for lunch compared with the low-fat breakfast. The free-choice lunch eaten after the MCT breakfast was also significantly smaller. Blood glucose and insulin concentrations were lower after the 3 fat breakfasts, followed by larger increases in glucose and enhanced insulin responses 30 min after the lunch. No differences were observed between the LCT-U and LCT-S conditions. We conclude that MCTs decreased food intake by a postabsorptive mechanism, although the exact effect of these lipids on carbohydrate oxidation will require further studies involving nutrient balance measurements.

Adult↗

Poor digestibility of fully hydrogenated soybean oil in rats: a potential benefit of hydrogenated fats and oils.

The digestibility and absorption of dietary triacylglycerols are dependent on a number of factors including their fatty acid profile. Data demonstrating poor bioavailability of dietary stearic acid would suggest that hydrogenated oil sources would have lower digestibility coefficients compared with their native oils. To test this hypothesis, postweanling rats were fed one of four diets, formulated to contain 40% of energy as fat (assuming complete bioavailability), for 14 d. The diets only differed by fat type, containing soybean oil (SBO), fully hydrogenated soybean oil (HSB), medium-chain triglyceride oil (MCT), or hydrogenated coconut oil (HCO). Rats fed HSB consumed more food during the last 6 d (155.2 +/- 2.7 g) than those in each of the other groups (MCT: 118.9 +/- 2. 2 g; HCO: 124.7 +/- 3.2 g; SBO: 123.8 +/- 2.3 g), yet, they did not gain more weight. Two-day fecal excretion was almost three times greater in HSB-fed rats than in rats fed any other diet (P < 0.0001) because HSB was very poorly available. The digestibility coefficients (a measure of bioavailability) of the four fats were: HSB (30.9 +/- 1.3%) < HCO (94.5 +/- 0.4%) < SBO (97.0 +/- 0.4%) < MCT (98.7 +/- 0.2%) (P < 0.0007). All rats compensated for the incomplete availability of the fats, as apparent absorbable energy consumed did not differ among diet groups. The present data suggest that HSB only contributes 11.6 kJ/g (most fats contribute approximately 37.7 kJ/g) and that not only manufactured fat substitutes, such as olestra, but also more conventional fats are incompletely available to the body. Foods that currently contain HSB may contribute much less utilizable fat and energy than presently realized.

Animal Nutritional Physiological Phenomena↗

Nutritional implications of microparticulated protein.

Recent technological developments have permitted the large-scale preparation of ingredients enriched with microparticulated proteins (MPP) that can be used to replace much or essentially all of the fat in a variety of traditional, full-fat foods. These include ice cream, salad dressings, mayonnaise and cheese spreads. In this paper we consider the nutritional implications of MPP, beginning with an assessment of the need for a fat-substitute and then the potential impact of MPP on the fat content of applicable foods and on the diet as a whole. Under projected conditions of maximum use of these MPP-containing foods by the consumer, the mean reduction in the fat content of the "current U.S. diet" would be about 14%. Although not dramatic, this represents a significant move in the direction of dietary changes that have been recommended by national and international authorities concerned with diet-health relationships. The risk/benefit ratio associated with inclusion of MPP in the diet is considered to be very high. This new development by the food industry is of considerable scientific interest and of potential practical importance for the nutrition and well-being of our society.

Dietary Fats↗

MRI assessment of right ventricular dysplasia.

Right ventricular dysplasia is a new entity of unknown origin in the classification of cardiomyopathies. Also known as arrhythmogenic right ventricular cardiomyopathy (ARVC) or arrhythmogenic right ventricular dysplasia, it is a disease of the heart muscle characterised by fibroadipose atrophy mainly involving the right ventricle and responsible for severe ventricular arrhythmias and sudden death also in young people. Magnetic resonance imaging provides evidence of ventricular dilatation at the outflow tract, thinning and thickening of the wall, diastolic bulging areas (especially located at the level of the right ventricle outflow tract) and fatty substitution of the myocardium mainly at the level of the right ventricle. Many radiologists erroneously consider the previously described fatty substitution as the main sign of ARVC, even though an evaluation of fat substitution alone may be a source of error for two reasons: firstly, because isolated areas of fatty replacement are not synonymous with ARVC since small non-transmural focal fatty areas of fat are also present in the normal patients; and secondly, because the MRI detection of fat may be overestimated due to partial-volume artefacts with normal subepicardial fat. Cardiac MRI can also be employed for the diagnosis of idiopathic right ventricular outflow tract tachycardia. Considering the evolutive nature of the disease, the non-invasiveness of MRI allows the follow-up of these patients and may be considered an excellent screening modality for the diagnosis of ARVC in family members. Finally, MRI can be employed in electrophysiological studies to locate the arrhythmogenic focus and reduce sampling errors.

Adipose Tissue↗

Synthesis and estimation of calorific value of a structured lipid-potential reduced calorie fat.

The majority of reduced calorie fats and fat substitutes available today, though similar in texture and flavor to natural fats, contain fatty acids that are not usually present in edible oils and fats and thus do not fully match the chemistry and functions of natural fats. For example, such products do not provide nutritionally important essential fatty acids (EFA). In this investigation, we prepared and evaluated a reduced calorie fat, prepared entirely from natural fats, taking advantage of the fact that long-chain saturated fatty acids (LCSFA), such as behenic acid (22:0), are poorly absorbed. Mustard oil (MO) and sunflower oil (SO) were used as substrates to yield a structured lipid (SL). The product, being derived from a natural vegetable oil, would thus provide EFA, as would a native fat, a feature not provided by the low-calorie fats available in the market. Erucic acid (22:1) was isolated from MO by a lipase (EC 3.1.1.3)-catalyzed reaction. It was then hydrogenated to behenic acid, the ethyl ester of which was subsequently enzymatically transesterified with SO to yield a plastic fat containing about 30-35% behenic acid. Absorption of this fat was studied in Wistar rats. In a preliminary single oral dose experiment, rats were fed equal amounts (2 mL) of SO and the SL. Plasma triacylglycerol (TAG) levels were estimated after 1, 2, and 3 h of feeding. The significantly lower concentration of plasma TAG in the 2-h sample, observed in the SL-fed group compared to the SO-fed group (P<0.001), indicated poor absorption of the SL. In order to estimate the calorific value of the SL, we conducted a restricted diet growth experiment over 21 d on weanling Wistar male rats with SO as caloric control. Diets for the test groups were modified by adding 5, 10, and 15% SO for the control groups, and 5 and 10% SL for the experimental groups. Food consumption of the test groups was restricted to 50% of the feed containing 5% SO that had been consumed by the ad libitum group the previous day. Body weights were recorded during the experiment. Calorific value of the SL was estimated by comparing the 21 st-d mean body weight gain of the control group with that of the experimental group. Estimated calorific value of the SL was 5.36 kcal/g. Most of the behenic acid fed was excreted, as indicated by the analysis of the fatty acids of plasma and fecal total lipid. A second growth experiment on ad libitum diet was conducted over 21 d on weanling Wistar male rats to compare the absorption behavior of the SL with that of natural oil. SO (10%) was added to the diet of the control group, and SL (10%) was added to the diet of the experimental group. Feed consumption, as well as body weights, was recorded during the experiment. The growth pattern of the experimental group was identical to that of the control group during the period of study. The mean feed intake (9.8 g/d/rat for the control group vs. 9.9 g/d/rat for the experimental group) indicated good palatability of the product. In conclusion, the enzymatically synthesized SL containing EFA and natural antioxidants has nutritional properties almost identical to those of natural fats, and can be used as a reduced calorie fat.

Animals↗

Familial concordance of dietary fat practices and intake.

This study examined parent and child dietary fat practices and child dietary fat intake. High- and low-fat practices and percentage of kilocalories from fat were obtained from food records completed by 132 students in the 4th to 6th grades. Parents completed three scales: meat modifications (MMOD); fat substitutions (FSUB); and fruit, juice, and vegetable practices (FJVP). A parent low-fat practices (PLFP) scale was created with the items matching the child low-fat practices (LFPs). Parent PLFP, FSUB, and FJVP were significantly correlated with child LFPs. Parent LFP was a significant predictor of child LFP. Family intervention programs targeting dietary fat behaviors should encourage use of low-fat dietary behaviors.

Adult↗

Low-energy substitutes for sugars and fats in the human diet: impact on nutritional regulation.

Low-calorie substitutes for dietary sugars and fats are offered to the public as aids in the control of body weight. Their actual influence on food intake and energy regulation has been studied in many acute and longer-term studies. Artificial sweeteners are often presented as preloads, and their effects on subsequent intake are compared to those of sugars or nonsweet vehicles. Preloads are often liquid (drinks) or semisolid (yogurts) and presented as snacks, rather than parts of a meal. Under these conditions, partial or complete compensation for the missing energy is observed most often over the course of a few hours. However, increases in appetite have also been reported. Low-energy fat substitutes also apparently allow energy, but not nutrient (fat) compensation. Short-term, medium-term, and long-term behavioural responses to the use of low-energy substitutes can be different, mainly as a result of learning. Consequently, effects of their chronic use on body weight, body composition, nutritional balance, and various physical parameters are only partially predictable on the basis of present knowledge. The present article reviews recent contributions to this field and delineate open areas of research.

Body Weight↗

Effects of dietary fat on incidence of spontaneous and induced cancer in mice.

A study was done to evaluate the effect of quantity and degree of saturation of dietary fat on the incidence of spontaneous tumors in male and female Swiss mice and in female C3H mice and on the incidence of tumors induced by s.c. administration of 1,2-dimethylhydrazine (DMH) in Swiss mice. Diets contained 5 or 17% fat substituted isocalorically for sucrose in a semipurified diet. Gross autopsy results suggest that the quantity of dietary fat, when fed isocalorically, did not appreciably influence the incidence of spontaneous or DMH-induced tumors in these mouse strains. Mice fed 17% of the triene fat generally had a higher incidence of liver tumors than corresponding groups fed the saturated fat. High levels (0.5%) of butylated hydroxyanisole protected female C3H mice from spontaneous liver tumors, but low levels of butylated hydroxyanisole (200 ppm of fat) did not protect. Neither level of butylated hydroxyanisole influenced tumor incidence in CD-1 mice. The absence of gross bowel tumors in animals given DMH was unexpected but may be related to the levels of cholesterol and fiber in the diets, since these factors are reported to influence the effects of DMH.

Animals↗

The effect of vegetable oil-based cheese on serum total and lipoprotein lipids.

OBJECTIVE: To investigate the effect of rapeseed oil-based cheese (milk-fat substituted by rapeseed oil) on serum total and lipoprotein lipid concentrations and blood pressure in reference to ordinary, milk-fat-based cheese in subjects with mildly to moderately elevated serum cholesterol concentration. DESIGN: Randomized, controlled, single-blind, cross-over clinical trial. SETTINGS: Outpatient dietary intervention with free-living subjects in Eastern Finland. INTERVENTIONS: The study began with a 2 week pre-trial period followed by two 4 week intervention periods. During the intervention study subjects replaced their ordinary cheese or cold cuts with 65 g of rapeseed oil-based or milk-fat-based control cheese. The type of test cheese was switched at 4 weeks of intervention. Altogether 31 subjects completed the study. RESULTS: Compared with the control cheese period the mean serum total cholesterol concentration was 6.7% (95% Cl -9.9 to -3.5%) lower after 2 weeks and 5.0% (95% Cl -7.5 to -2.5%) lower after 4 weeks of use of rapeseed oil-based cheese. Respectively, LDL cholesterol concentration was 7.0% (95% Cl -11.7 to -2.6%) lower after 2 weeks use and 6.4% (95% Cl -10.0 to -2.8%) lower after 4 weeks' use of rapeseed oil-based cheese. CONCLUSIONS: The present study showed that the rapeseed oil-based cheese reduces serum total and LDL cholesterol concentrations in mildly to moderately hypercholesterolemic subjects when replacing ordinary milk-fat-based cheese in the diet. SPONSORSHIP: Mildola Ltd, Tuusula, Finland and Kyrönmaan Juustomestarit Ltd, lsokyrö, Finland.

Adult↗

The effect of non-absorbable fat on energy and fat intake.

One of the main issues with respect to the usefulness of fat-replacers is their effectiveness. The question is whether or not people compensate for the "missing" energy due the replacement of fat by the fat-substitute. The present paper is concerned with the results of a number of studies carried out on the effects of the fat-replacer sucrose-polyester on food intake. Sucrose-polyester (SPE) is a substance with similar sensory and physical-chemical properties as fat, but it contains no metabolizable energy, because it is not digested in the human gastrointestinal tract. In the first two short-term studies, we replaced the fat by SPE in croissants. Thirty-three subjects in the first study and 34 subjects in the second study consumed 2 1/2 croissants, either with fat or SPE. After ingestion they rated subjective feeling of hunger, and recorded their ad libitum food intake. The results of both studies showed that the croissants with SPE had a similar satiating effect as the croissants with fat. In two subsequent short-term studies, we added either fat, SPE or water to warm meals served as lunch. The high water and high SPE lunches contained about 450 kcal, whereas the high fat lunches contained about 900 kcal. After ingestion of the lunches, subjects (39 in study 3; 35 in study 4) recorded their feelings of hunger. Two hours after the lunches, subjects were presented with an attractive buffet from which they could eat ad libitum. The results showed that hunger and food intake were similar after the water, SPE and fat lunches. The subjects did not detect the 450 kcal energy difference in the lunches. The last two studies with SPE lasted for 12 days. The results of these two longer-term studies were similar to the results of the short-term studies. There was little energy compensation and no fat compensation. It is concluded that fat replacers can be helpful in reducing fat and energy intake.

Adult↗

Nonabsorbable fat (sucrose polyester) and the regulation of energy intake and body weight.

A substantial number of people have difficulties in controlling their body weight and energy/fat intake. Fat substitutes may be helpful in solving these problems. We here report the first study on the longer-term effects of the nonabsorbable fat sucrose polyester (SPE) on energy intake in normal-weight subjects. We studied the longer-term (12 days) effects of the consumption of warm meals with normal dietary fat (5.0 MJ, 1,195 kcal) or meals in which 52 g of fat were replaced by the fat replacer SPE (3.1 MJ, 740 kcal) on spontaneous food intake (measured by dietary records), body weight, and gastrointestinal complaints in healthy volunteers in two studies. In the first study the 48 subjects were unaware of the treatment, whereas in the second study the 47 subjects were informed of what they received. In both studies men and women consumed less energy per day during the SPE (11.2 MJ) compared with the fat treatment (12.7 MJ) (P values < 0.0001) for the whole 12-day period. This was accompanied by equivalent changes in body weight. The percentage of energy from fat decreased from 43% during the fat treatment to 32% during the SPE treatment. During the SPE treatment, more gastrointestinal complaints and a higher frequency of defecation were reported. Information about the treatment did not affect. the outcomes. It is concluded that the use of a fat replacer such as SPE helps in reducing fat and energy intake in normal-weight people.

Adult↗

[Non-caloric compounds with fat-like functional properties (pseudofats)].

The review deals with the synthesis, characterization, physicochemical and physiological properties with respect to nutrition of acaloric fat-like compounds (pseudofats) with special regard to fatty acid esters of sucrose, glycerol ethers and glycerol dicarbonic acid esters. Furthermore an outlook is given of other classes of compounds that are potentially suited to substitute fat as for instance polycarbonic acid-, polyglycerol-, and polyglycol derivatives.

Chemical Phenomena↗

Obesity in evolutionary perspective.

Man is the only primate without fur. Hence subcutaneous fat constitutes the only means of insulation. For an endothermic animal such as man, whose tissues are susceptible to temperature fluctuations, an efficient means of insulation provided by subcutaneous fat not only conserves energy but also facilitates thermal regulation. The development of physiological mechanisms for accurate thermal regulation may be the basis of man's relatively long life-span. Why Homo sapiens, alone among the primates, substituted fat for fur as insulation is not know, but one plausible explanation may be the adoption of a semi-aquatic style of living during evolutionary development. Whatever the reason, subcutaneous fat is an important organ, and the level of adiposity is subjected to fine control by sophisticated physiological mechanisms. Thus, in healthy individuals, body fat content is a reflection of physiological requirements, and dietary and other measures for weight reduction may be detrimental to health. The time has come for the formation of a Fat Liberation Movement.

Adaptation, Physiological↗

Diurnal feeding and drinking patterns of adult cats as affected by changes in the level of fat in the diet.

A continuous on-line computerized monitoring system was used to measure food and water intake patterns of mature cats during consecutive low-fat (3 week) or high-fat (3 week) feeding. Cats consumed less of the high-fat than the low-fat diet such that their mean daily gross energy intake was the same for both diets. It was concluded that cats regulate their daily food intake on the basis of energy density. High-fat substitution caused a reduction in the quantity of food consumed in the dark cycle. There was no apparent change in either the light- or dark-cycle meal frequency, both the light- and dark-cycle average meal size were curtailed. Water intake did not vary significantly between low- and high-fat diets. There was no significant difference in number of drinking bouts or average bout volume for the low- and high-fat diets in both the light and dark cycles. Two diet-choice trials produced no clear preference for the low- or high-fat diet. It appears that the fat content, independent of flavor components or physical consistency, has little effect on dietary preference of the cat.

Animals↗

Severe 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) intoxication: kinetics and trials to enhance elimination in two patients.

In spring 1998, two women were diagnosed with severe 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) intoxication. Over the following 3 years, TCDD levels were monitored under various attempts to enhance its elimination, and the half-lives were evaluated. Olestra, a non-digestible, non-absorbable dietary fat substitute, was continuously administered to the patients either as pure substance or in potato-chips. Additionally, in the more severely contaminated patient, we studied whether low-density lipoprotein (LDL)-apheresis, an extracorporeal means of blood lipid elimination, was effective in reducing the TCDD body burden. The blood concentrations initially measured in spring 1998 were 144,000 pg/g blood fat in patient 1 and 26,000 pg/g in patient 2, the highest levels ever measured in adults. In March 2001, concentrations in blood fat were 35,900 and 9,500 pg/g, corresponding to overall elimination half-lives of 560 days (1.5 years) in patient 1 and 1050 days (2.9 years) in patient 2, which are considerably shorter than median values of 7-9 years reported for background and moderate exposure levels. Calculations of the TCDD half-lives and measurements of TCDD elimination via different routes allowed the calculation of an unidentified route of elimination, representing 78 and 62% of the overall elimination in patient 1 and 2, respectively, probably due to an induced hepatic metabolism caused by the high TCDD exposure. As previously reported, administration of olestra was found to be effective in increasing the fecal excretion of TCDD. Due to the short half-lives in our patients, the effect of olestra on the overall elimination was relatively small, but is expected to be much greater for 'normal' half-lives. LDL-apheresis was shown to eliminate TCDD, corresponding to the eliminated blood fat. When employed twice a week, the amount of TCDD excreted by this method was comparable to fecal excretion. In view of costs and time involved, LDL-apheresis does not seem to be justified for enhancement of TCDD elimination.

Adult↗