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American Journal of Clinical Nutrition, Vol. 71, No. 3, 807-815, March 2000
© 2000 American Society for Clinical Nutrition

Original Research Communications

Altered lipid profile, lipoprotein composition, and oxidant and antioxidant status in pediatric Crohn disease1,2,3

Emile Levy, Yasmine Rizwan, Louise Thibault, Guy Lepage, Sylvain Brunet, Lise Bouthillier and Ernest Seidman

1 From the Gastroenterology-Nutrition Unit, Centre de Recherche, Hôpital Sainte-Justine, Departments of Pediatrics and Nutrition, Université de Montréal.

2 Supported in part by grants from the Canadian Foundation for Crohn's and Colitis and by the George Weston Foundation and by research scholarship awards from Le Fonds de la Recherche en Santé du Québec (to EL and ES).

3 Address reprint requests to E Levy, GI-Nutrition Unit, Hôpital Sainte-Justine, 3175 Côte Ste-Catherine Road, Montreal, Quebec H3T 1C5, Canada. E-mail: levye{at}justine.umontreal.ca.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Growing evidence supports a role for peroxidation in the pathogenesis of Crohn disease (CD). The activation of inflammatory cells, the release of their mediators, and the excessive production of free radicals may affect circulating lipids.

Objective: We examined the lipid profile, lipoprotein composition, and oxidant-antioxidant status of children with CD.

Design: We studied 22 pediatric CD patients and 10 healthy control subjects.

Results: The proportion of saturated and monounsaturated fatty acids in plasma of CD patients was higher but that of polyunsaturated fatty acids was lower than in control subjects. This resulted in higher ratios in CD patients of palmitoleic acid to linoleic acid (P < 0.05) and of eicosatrienoic acid to arachidonic acid (P < 0.04), 2 established indexes of essential fatty acid deficiency. Hypocholesterolemia was noted in CD patients as a result of lower LDL-cholesterol concentrations than in control subjects (P < 0.02). Plasma apolipoproteins B (P < 0.02) and A-I (P < 0.02) were also lower in CD patients, whereas plasma triacylglycerols were higher (P < 0.005). Lipoprotein composition was altered in CD patients, with relative triacylglycerol depletion and protein enrichment in VLDL. In contrast, intermediate-density lipoprotein of CD patients was characterized by an increased percentage of triacylglycerol and protein (P < 0.005) and a reduced proportion of phospholipids (P < 0.01). Additional abnormalities were observed in the chemical distribution of HDL2 and HDL3 moieties. Lipid peroxidation was documented by higher plasma malondialdehyde concentrations in CD patients (P < 0.05), accompanied by lower retinol concentrations (P < 0.02).

Conclusion: Disturbances in the lipid profile, in lipoprotein concentrations and composition, and in oxidant-antioxidant status occur in CD patients.

Key Words: Crohn disease • reactive oxygen metabolites • lipids • lipoproteins • antioxidants • peroxidation • children


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Crohn disease (CD) is a chronic inflammatory bowel disease that can affect any region of the gastrointestinal tract. Most commonly, the inflammation involves the distal small bowel, often including segments of the proximal large intestine as well (1, 2). Although the etiology of CD remains unknown, pathogenetic factors implicated include microbial agents, immune dysfunction, genetic susceptibility, and various environmental factors such as diet (2–4). A growing body of evidence suggests that uptake of luminal antigens across the mucosal epithelium elicits an aberrant immune response, culminating in intestinal inflammation, local peroxidation, and systemic circulation of inflammatory cytokines and mediators (5). These disturbances are often associated with malnutrition secondary to reduced dietary intake and malabsorption, potentially impairing essential polyunsaturated fatty acid (PUFA) and antioxidant status, as well as the composition of lipoprotein particles. The impairment of lipoprotein particles is of particular significance because they efficiently transport large amounts of fat and lipid-soluble vitamins in the circulation. Lipoproteins also contribute to the maintenance of cellular membrane structure and function.

Disturbances in lipoproteins resulting from peroxidative attack may affect their normal metabolism and the subsequent distribution of both lipid and vitamin moieties to peripheral organs. Whereas inconsistent data on these indexes are available for adults (6–10), little information has been reported for the pediatric age group, although children and adolescents account for 25% of all new cases of CD (1). Furthermore, no thorough investigation of lipoprotein composition, in which lipid and apolipoprotein moieties are characterized, has been carried out in persons with CD. Therefore, the aim of this study was to examine the fatty acid distribution, lipid profile, lipoprotein composition, and concentrations of antioxidants and oxidants in children with CD.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects
Twenty-two patients with CD were recruited from the inflammatory bowel disease clinic at Sainte-Justine Hospital. The diagnosis of CD was based on standard clinical, radiographic, colonoscopic, and histologic features (2). The severity of the disease was evaluated by using the validated Crohn's Disease Activity Index (CDAI), which assesses the daily number of liquid or very soft stools, the severity of abdominal pain, general well-being, extraintestinal manifestations of the disease, ability to attend school and interact socially, the presence of an abdominal mass, hematocrit, and body weight (2, 11). Patients with CDAI scores >=150 are considered to have active disease. Energy intake was calculated from a 3-d food record and expressed as a percentage of the recommended nutrient intake for age (12). The patients' characteristics are presented in Table 1Go. At the time of testing, patients were treated with 5-aminosalicylic acid (orally, intrarectally, or both), 6-mercaptopurine, and metronidazole. No patients were receiving systemic corticosteroids or defined formula diets. Ten healthy children matched with the patients by age and sex served as control subjects. The study protocol was approved by the ethics committees of Sainte-Justine Hospital.


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  		TABLE 1.. Clinical characteristics of the pediatric Crohn disease patients1
 
Blood samples
Blood samples were collected in tubes containing 1 g EDTA/L after subjects had fasted for 12 h overnight. Plasma was separated immediately by low-speed centrifugation (700 x g for 20 min) at 4°C.

Fatty acid analysis
Fatty acids in whole plasma were assayed by an improved method described by us previously (13). Briefly, each sample to be analyzed was subjected to direct transesterification and then injected into a gas chromatograph (model HP 5880; Hewlett-Packard, Rockville, MD) by using a 60-m fused silica capillary column coated with SP 2331.

Lipoprotein isolation
Lipoprotein fractions were isolated by discontinuous density gradient ultracentrifugation in an L5-65 preparative ultracentrifuge (Beckman, Montreal) with a Ti-50 rotor as reported previously (14, 15). Briefly, after preliminary centrifugation to remove chylomicrons (41000 x g for 30 min at 4°C), VLDLs, intermediate-density lipoprotein (IDLs), and LDLs were isolated at densities of 1006 g/L, 1019 g/L, and 1063 g/L, respectively, by centrifugation at 100000 x g for 18 h at 5°C. HDL subpopulations were separated by centrifugation at 100000 x g for 48 h at 4 °C at the following densities: 1125 g/L for HDL2 and 1210 g/L for HDL3. The lipoprotein fractions were dialyzed intensively against 0.15 mol NaCl/L and 0.001 mol EDTA/L at pH 7.0.

Vitamin measurements
Vitamins were measured according to Lepage et al (16). Plasma samples were thawed in the dark and processed for analysis under subdued light. Aliquots (500 µL) of the different specimens were mixed for 30 s on a vortex mixer with 500 µL of an internal standard (12 µg tocopheryl acetate in anhydrous alcohol). After the addition of n-hexane (twice, 2.5 mL each), the tubes were shaken (10 min), sonicated (3 min), and centrifuged (5 min) at 1000 x g at 4 °C. The n-hexane layer was transferred to a tube and the pooled organic extracts of each sample were evaporated to dryness under a gentle stream of nitrogen at 20° C. After rapidly removing the tubes from the water bath, the residues were reconstituted with 150 µL acetonitrile:methylene chloride:methanol (70:20:10, by vol). After the addition of 25 µg ascorbic acid in 50 µL ethanol, the tubes were mixed in a vortex mixer (30 s) and sonicated (3 min). Aliquots (20 µL) were injected into the HPLC system.

The chromatographic analyses were performed on a model 1090 HPLC system (Hewlett-Packard, Montreal) with a spherical 5-µm C18 octadesilsilane Hypersil column (20 cm x 2.1 mm internal diameter; Hewlett-Packard). A guard column from the same package preceded the main column. This reversed-phase octadesilsilane column was used for the simultaneous determination of the fat-soluble vitamins by using isocratic elution with acetonitrile:chloroform:isopropanol:water (79:16:3.5:2.5, by vol). The flow rate was 300 µL/min. The light absorption of the compounds was measured with a photodiode-array detector at wavelengths of 282 nm for tocopheryl acetate, 290 nm for {alpha}-tocopherol, 322 nm for retinol, and 446 nm for ß-carotene. The amounts were calculated by using tocopheryl acetate as the internal standard. The areas under the curve of the chromatographic peaks were used for the calculations. All manipulations were carried out under subdued light to avoid photoisomerization of the compounds. The photodiode-array detector acquires chromatographic signals and spectra over the wavelength range of 190–600 nm.

Malondialdehyde and glutathione measurement
Plasma free malondialdehyde concentrations were measured according to a modified method of Chirico (17). Proteins were first precipitated with a 10%-NaSO4 solution. The protein-free supernate was then reacted with an isovolume of a 0.5%–thiobarbituric acid solution at 95°C for 30 min. After the reactions were cooled to room temperature, pink chromagene was extracted with n-butanol and dried over a stream of nitrogen at 37°C. The dry extract was then resuspended in a mobile phase of KH2PO4:methanol (70:30) before malondialdehyde detection by HPLC (18). Glutathione was measured by Tietze's technique (19).

Lipid and lipoprotein analysis
Plasma concentrations of total cholesterol, free cholesterol, and triacylglycerols were measured enzymatically with a commercial kit (Boehringer Mannheim, Montreal) as reported previously (14, 15). Cholesteryl esters were calculated as 1.7 times the difference between total and unesterified cholesterol. Lipoprotein protein was quantified according to Lowry et al (20) with bovine serum albumin as the standard. Phospholipids were measured by the Bartlett method (21). HDL cholesterol was measured after precipitation of VLDL and LDL with phosphotungstic acid (14, 15). The apolipoprotein composition of plasma lipoproteins was qualitatively assayed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The gels were stained for 1 h with Coomassie blue and destained in 7% acetic acid. The bands of apolipoproteins were identified by comparison with the mobility of apolipoprotein standards and different molecular weight standards. The densitometric distribution of apolipoproteins was assayed as described previously (14, 15).

Statistical analysis
All values are expressed as means ± SEMs. Statistical differences were assessed by Student's two-tailed t test. P values <=0.05 were considered significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Plasma lipids, lipoproteins, and apolipoproteins
Several differences were noted between the plasma lipids, lipoproteins, and apolipoproteins of the CD patients and control subjects (Figure 1Go). Mean triacylglycerol concentrations were higher in CD patients than in control subjects, whereas total cholesterol concentrations were lower. Total cholesterol was characterized by lower LDL-cholesterol concentrations in CD patients, with only a slight trend toward lower HDL-cholesterol concentrations. As anticipated in view of these findings, concentrations of apolipoproteins A-I and B were also lower in CD patients than in control subjects. We noted diminished intensity particularly in the ß-lipoprotein fraction (data not shown) with use of semiquantitative agarose gel electrophoresis,.



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  		FIGURE 1. . Mean (±SEM) plasma lipids, lipoprotein cholesterol, and apolipoproteins in fasting plasma of pediatric Crohn disease patients ({square}; n = 22) and age-matched control subjects ({blacksquare}; n = 10). TG, triacylglycerol; TC, total cholesterol; LDL-C, LDL cholesterol; HDL-C, HDL cholesterol; Apo, apolipoprotein. *,**,***Significantly different from control subjects: *P < 0.01, **P < 0.02, ***P < 0.005.

 
Fatty acid status
The plasma fatty acid profiles of the CD patients showed several significant differences compared with those of the age-matched control subjects (Table 2Go). The proportion of linoleic acid (18:2n-6), an essential fatty acid, was lower in CD patients. In contrast, the proportion of monounsaturated fatty acids was higher in CD patients. The overall percentages of the various species and the ratios of fatty acids relevant for the assessment of essential fatty acid deficiency are summarized in Table 3Go. Proportions of both total n-3 and n-6 PUFAs were lower in CD patients than in control subjects, whereas proportions of saturated and monounsaturated (n-7 and n-9) fatty acids were higher. The ratios of eicosatrienoic acid (20:3n-9) to arachidonic acid (20:4n-6) and of palmitoleic acid (16:1n-7) to 18:2n-6, established indexes of essential fatty acid status, were higher in CD patients than in control subjects, confirming essential fatty acid deficiency in the CD patients.


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  		TABLE 2 .. Plasma fatty acid profile in pediatric Crohn disease (CD) patients and age-matched control subjects1
 

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  		TABLE 3.. Proportions of fatty acid families and indexes of essential fatty acid deficiency and desaturase activity in plasma of pediatric Crohn disease (CD) patients and age-matched control subjects1
 
Lipoprotein composition
The chemical composition of plasma lipoproteins from the CD patients and control subjects is summarized in Table 4Go. The VLDL fraction of the CD patients contained less triacylglycerol and more protein than did the VLDL fraction of the control subjects. In IDL, the percentages of triacylglycerol and protein were higher for CD patients, whereas the phospholipid content was lower. No significant differences in the LDL fraction were noted between the 2 groups. The 2 HDL subpopulations also had lipoprotein disturbances in CD patients. Triacylglycerols, free cholesterol, and cholesteryl ester contents were higher in the HDL2 fraction of CD patients, whereas phospholipid and protein contents were lower. The marked differences in HDL3 composition between the groups consisted of a lower cholesteryl ester content concomitant with a higher phospholipid content in the CD patients. As expected from these changes in lipoprotein components, particle size was also affected in CD patients, as inferred from the mass ratio of core (triacylglycerol + cholesteryl ester) to surface (free cholesterol + lipoprotein protein + phospholipids) constituents. The calculated value of these ratios indicated that VLDL and HDL3 were smaller and IDL larger in the CD patients than in the control subjects. LDL and HDL3 particle sizes were not significantly different between CD patients and control subjects.


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  		TABLE 4.. Chemical composition of lipoproteins in pediatric Crohn disease (CD) patients and age-matched control subjects1
 
The distribution of apolipoproteins in the lipoprotein fractions, as assayed by gradient SDS-PAGE (4–15%) is shown in Figure 2Go. Except for the apolipoprotein E bands, there were no visible differences in VLDL apolipoproteins. There were also no consistent differences in the apolipoprotein B patterns of LDL. Apolipoproteins A-I and A-II in the HDL fractions, as determined by 15% SDS-PAGE, are also shown in Figure 2Go. Ratios of apolipoprotein A-I to A-II were higher in the HDL2 and HDL3 fractions of the CD patients.




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  		FIGURE 2. . Apolipoprotein profile of plasma lipoproteins in pediatric Crohn disease patients (P) and age-matched control subjects (C). Lipoproteins were isolated by ultracentrifugation, delipidated, and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Purified apolipoproteins (A-I and A-II) and molecular weight standards (MW) were used as reference proteins. The molecular weight standards were as follows: phosphorylase B (97400), bovine serum albumin (66200), ovalbumin (46000), carbonic anhydrase (30000), trypsin inhibitor (21500), and lysozyme (14300). CS, apolipoprotein C isoforms.

 
Oxidant-antioxidant status
To assess the antioxidant status of CD patients, their plasma retinol, ß-carotene, vitamin E, and {gamma}-tocopherol concentrations were measured and compared with those in control subjects (Figure 3Go). Only retinol concentrations were observed to be significantly lower in CD patients. Circulating concentrations of glutathione, a key endogenous soluble antioxidant, were higher in CD patients than in control subjects (Figure 4Go). Additionally, increased oxidative stress was observed in the CD patients, as evidenced by 70% higher malondialdehyde concentrations than in the control subjects.



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  		FIGURE 3. . Mean (±SEM) vitamin concentrations in fasting plasma of pediatric Crohn disease patients ({square}; n = 22) and age-matched control subjects ({blacksquare}; n = 10). *Significantly different from control subjects, P < 0.02

 


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  		FIGURE 4. . Mean (±SEM) malondialdehyde and glutathione concentrations in plasma of pediatric Crohn disease patients ({square}; n = 22) and age-matched control subjects ({blacksquare}; n = 10). *Significantly different from control subjects, P < 0.05.

 
Effect of disease activity on nutritional status
The CD patients were classified according to whether they had active or quiescent disease on the basis of their CDAI scores (Table 5Go). Although differences were observed between the 2 groups of patients in terms of mean energy intake and nutritional status, these were not significant. Furthermore, concentrations of both glutathione and malondialdehyde tended to be higher in the subgroup with active disease, but not significantly so. Fatty acid compositions were also examined in the 2 subgroups of CD patients (Table 6Go). There were no significant differences between subgroups in the various species and families of fatty acids or in the ratios of fatty acids relevant for assessing essential fatty acid deficiency.


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  		TABLE 5.. Comparison of clinical and nutritional indexes in pediatric Crohn disease patients with active and inactive disease1
 

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  		TABLE 6 .. Comparison of proportions of fatty acid families and indexes of essential fatty acid deficiency and desaturase activity in plasma of pediatric Crohn disease patients with active and inactive disease1
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The present study identified important alterations in the lipid profile, lipoprotein composition, and oxidant-antioxidant status of pediatric patients with CD. Compared with age-matched, healthy control subjects, CD patients had abnormal fatty acid status characterized by lower concentrations of n-3 and n-6 fatty acids in plasma and higher proportions of the n-7 and n-9 species. These changes resulted in higher ratios of 16:1n-7 to 18:2n-6 and of 20:3n-9 to 20:4n-6 in CD patients, indicating essential fatty acid deficiency. Our data also documented abnormally low plasma concentrations of LDL cholesterol and apolipoprotein B in CD patients, with a concomitant rise in triacylglycerol. Additionally, all lipoprotein fractions in CD patients, except LDL and HDL3, had abnormal chemical compositions and sizes. We found no association between lipid or lipoprotein alterations and disease activity. Finally, the altered oxidant-antioxidant status of CD patients was shown by lower plasma retinol concentrations, higher glutathione concentrations, and higher plasma malondialdehyde concentrations than in control subjects. This last finding is consistent with abnormal lipid peroxidation in the circulation of CD patients.

PUFAs play important roles in cell membrane function and eicosanoid synthesis (22, 23). PUFA depletion in CD patients is predictable, given these patients' high demand for intestinal tissue repair and the heightened conversion of PUFAs into eicosanoids (24), key mediators of inflammation. However, contradictory findings concerning long-chain PUFAs in CD were reported previously. Decreased, normal, and increased proportions of n-3 and n-6 fatty acids compared with those in healthy subjects have been observed (7, 9, 25). In the present study, in which we used technologic refinements of gas-liquid chromatography such as direct transesterification and separation of fatty acids on a 60-m capillary column (13), we detected abnormal PUFA concentrations in pediatric CD patients. The low concentrations of the n-3 and n-6 families concomitant with the higher concentrations of the n-7 and n-9 species resulted in higher ratios of 16:1n-7 to 18:2n-6 and of 20:3n-9 to 20:4n-6 in CD patients. Although the magnitude was not as extreme as we reported in patients with cystic fibrosis (14, 26), our data show that CD patients are vulnerable to essential fatty acid deficiency. Contributing risk factors may include fat malabsorption, hypermetabolism, and inadequate nutritional intake. In this study, the mean energy intake of the CD group was in fact lower than the age- and sex-specific Canadian recommended nutrient intake (27).

Abnormal fatty acid concentrations were detected in leukocytes from adult patients with CD without essential fatty acid deficiency (28, 29). Furthermore, Esteve-Comas et al (6) found that patients with active inflammatory bowel disease had elevated plasma concentrations of {alpha}-linolenic acid (18:3n-3) and docosahexaenoic acid (22:6n-3), only small changes in 18:2n-6, and a decreased proportion of dihomo-{gamma}-linolenic acid (20:3n-6) compared with healthy subjects. The inconsistent results of the various studies reported to date may be due to methodologic differences, the activity or extent of the disease in the patients studied, or the patients' variable nutrient intake. In addition, as hypothesized by some investigators, increased biosynthesis might be the cause of the high proportions of PUFA compounds in adults (6), a situation that is at variance with that observed in children. The evaluation of essential fatty acid status in patients with CD may be clinically useful because therapeutic trials have shown beneficial effects of supplementation with n-3 fatty acids (30).

To date, little information is available on the plasma lipid profile, lipoprotein composition, or apolipoprotein concentrations of patients with CD. Although our findings disclose various changes in these biochemical indexes, no obvious associations were noted between these disturbances and selected clinical aspects of the patients, such as disease activity, site of disease, surgical history, or current medications. Furthermore, none of our older patients smoked or consumed alcohol, 2 factors that may influence antioxidant and lipoprotein status in adults.

Evidence from our clinical and experimental studies carried out previously suggests that essential fatty acid deficiency and malnutrition can negatively affect both the intestinal absorption of fat and lipoprotein metabolism (14, 26, 31–33). At this time, it is uncertain whether the hypocholesterolemia noted in CD patients results from intestinal malabsorption or malnutrition. Similarly, further work is needed to explore whether the hypertriglyceridemia in CD patients is a consequence of high carbohydrate consumption (34).

CD is characterized by increased chronic inflammatory cell infiltrates in the mucosal lesions. The excessive local production of soluble mediators from activated monocytes and polymorphonuclear leukocytes has been implicated in mediating the tissue injury (35). Important among these mediators are oxygen free radicals. The chronic gut inflammation promotes an imbalance between oxidant and antioxidant mechanisms at the tissue level (36) and may even compromise circulating antioxidant concentrations. In this respect, the plasma concentrations of ascorbic acid, vitamin E, and ß-carotene were reported to be significantly lower in CD patients than in adult control subjects, despite multivitamin supplementation (37, 38). However, children with CD were reported to have higher plasma antioxidant concentrations than healthy children (10). In the present study, we did not observe alterations in vitamin E, ß-carotene, or {gamma}-tocopherol concentrations in the CD patients. However, retinol concentrations were significantly lower in CD patients than in control subjects, consistent with other reports in adults with CD (38, 39). These inconsistencies in reports of circulating antioxidants to date may be due to the patients' degree of inflammation, the patients' medication and supplement use, enteric losses, altered mobilization as a result of inflamed mucosa, malabsorption, and decreased nutrient intake. In view of the risk for physiologic sequelae associated with vitamin A deficiency, special attention should be devoted to retinol status in CD.

Glutathione is an important intracellular antioxidant. This tripeptide helps to detoxify free radicals, peroxides, and electrophilic compounds of endogenous and exogenous origin (40, 41). Interestingly, glutathione content in red blood cells was higher in our CD patients than in control subjects, consistent with the pediatric study by Hoffenberg et al (9). Additional investigation is needed to verify whether the high values of glutathione constitute an adaptive response to the increased oxidative stress. Although it is difficult to extrapolate from an experimental model, we obtained similar results in animals exposed to oxidative stress by iron-induced lipid peroxidation (18). These high concentrations of glutathione may help prevent oxidation of {alpha}-tocopherol (42) and preserve ascorbic acid concentrations (43).

Free radicals are known to occur as natural byproducts under physiologic conditions. However, their overproduction has been implicated in the pathogenesis of gut inflammation and intestinal injury in inflammatory bowel disease (36, 37). Oxyradical-induced cytotoxicity gives rise to lipid peroxidation through the reaction of free radicals and peroxides with PUFAs in cellular membranes, resulting in malondialdehyde formation. CD patients had significantly higher circulating malondialdehyde concentrations than did control subjects in the present study. It is unclear whether the excess malondialdehyde was generated in the patients' blood or was produced by the inflamed intestine and translocated into the circulation. The presence of malondialdehyde in the circulation may explain the noted reduction in essential fatty acids and the increased formation of glutathione as a means of preventing oxidative damage. Our previous studies of various disorders such as cystic fibrosis clearly established a relation between malnutrition, malabsorption, and essential fatty acid deficiency on the one hand and a defective lipid profile and lipoprotein composition on the other (14, 26, 44–46). Moreover, we showed that proinflammatory cytokines can adversely affect lipoprotein metabolism (47). For example, tumor necrosis factor {alpha} and interleukin 6 were shown to affect intestinal fat handling and lipid metabolism (47, 48). These factors are produced in excess in CD (4, 49). Nevertheless, our data failed to show an effect of disease activity on these indexes, likely because of the relatively small number of CD patients in the subgroups with active and quiescent disease. Further studies are required in which these indexes are analyzed serially in a cohort of CD patients over time.

In conclusion, we found substantial abnormalities in the concentrations of plasma lipids, malondialdehyde, and antioxidants and in the fatty acid and lipoprotein compositions of pediatric patients with CD. Although these abnormalities are not unique to CD, the occurrence of essential fatty acid deficiency is of concern, especially in the context of our current understanding of essential fatty acids in human biology. Supplementation with these fatty acids can meet the increased demand for tissue repair and membrane formation and prevent suboptimal cell function, malabsorption, and inadequate growth. Moreover, in view of the reduced antioxidant defense capacity and the presence of excessive lipid peroxidation, strategies should be elaborated to bolster the antioxidant system in pediatric patients with CD. Finally, further investigation is required to elucidate the mechanisms involved in the aforementioned abnormalities.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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Received for publication March 26, 1999. Accepted for publication July 9, 1999.




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