Fat-soluble Vitamin Levels Research Articles

Dietary decontaminated fish oil has no negative impact on fish performance, flesh quality or production-related diseases in Atlantic salmon (Salmo salar)

Fish oil is the main contributor of persistent organic pollutants (POPs) in fish feed. A combination of active carbon filtration and steam deodourization can remove most of the POPs. However, other fat soluble compounds are also removed, thus possibly affecting the nutritional quality of decontaminated fish oils. Sea water–adapted Atlantic salmon were fed 18 months a commercially relevant diet based on either decontaminated or non-treated fish oil until market size. The development of production-related diseases (fin/skin erosion, bone deformity, cataract) and fillet quality parameters (gutted weight, fillet fat soluble vitamin levels and fatty acid composition, colour, gaping, texture and sensory quality) were assessed. No significant differences in growth performances, feed conversion ratio or quality parameters between the two dietary groups were found. The fillet levels of fat soluble vitamins in market size fish remained unaltered, and only marginal differences were observed in fatty acid profiles. There was a significantly lower percentage of deformed vertebrae in the tail region of fish fed the decontaminated fish oil diets, indicating a positive effect of the use of decontaminated fish oil. No apparent negative effects of the use of decontaminated fish oil in Atlantic salmon diets were reported in this study.

Deficiencies in fat‐soluble vitamins in long‐term users of somatostatin analogue

Somatostatin analogues are administered to control hormone hypersecretion in acromegaly and carcinoid patients. Somatostatin analogues can increase fat in the stools, which can lead to loss of fat-soluble vitamins. The effect of long-term somatostatin analogue use on vitamin levels remains unknown. To investigate the prevalence of fat-soluble vitamin deficiencies in long-term somatostatin analogue users. All acromegaly and carcinoid patients using somatostatin analogues for ≥ 18 months visiting the University Medical Center Groningen between December 2008 and April 2009 were eligible. Vitamin levels of fat-soluble vitamins in blood, clinical and vitamin-dependent laboratory parameters were collected. In all, 19 acromegaly and 35 carcinoid patients were included. Twelve patients experienced steatorrhoea; two carcinoid patients experienced night blindness. Forty-two (78%) were deficient for one or more vitamins, and 32% (n = 17) had multiple deficiencies. Deficiencies for vitamin A, D, E, K1 and E in erythrocytes occurred in 6%, 28%, 15%, 63% and 58% of the patients. Prevalence of vitamin D, E and K1 deficiencies was similar in both patient groups. Treatment duration did not influence vitamin levels. The length of intestinal resection and age correlated negatively with vitamin A levels. Fat-soluble vitamin deficiencies are frequent during long-term somatostatin analogue treatment. Therefore, fat-soluble vitamins should be monitored in these patients.

Agenesis of the Dorsal Pancreas with Cat Eye Syndrome in an Adolescent Presenting with Abdominal Pain and Pancreatitis

Purpose: Case Report: A 17-year-old female with prior diagnoses of Cat Eye Syndrome (CES) and Ehlers-Danlos Syndrome (EDS) Type 1 presented with chronic abdominal pain. Seven weeks prior to presentation she was diagnosed with pancreatitis with an elevated lipase level. CT and ultrasound studies at that time revealed an atrophied and partially fat-replaced pancreas. On presentation at our institution her amylase and lipase were within normal limits however on review of the prior images it was found that the body and tail of the pancreas were absent. An MRCP with secretin revealed an abnormally formed head, neck and proximal body of the pancreas with an absent distal body and tail. There was a small caliber main pancreatic duct but no dilated side branches of the pancreatic duct or calcifications. The gall bladder and intra/extrahepatic bile ducts appeared normal. Secondary to the association of CES with malrotation, an upper GI barium study was obtained and was normal. Fat-soluble vitamin levels were normal. Investigations to rule out autoimmune pancreatitis, cystic fibrosis and diabetes mellitus were normal. Conclusion: We describe an adolescent with CES and EDS with newly diagnosed agenesis of the dorsal pancreas (ADP). This is a rare anomaly with 54 reported cases - predominantly in adults. ADP results from developmental failure of the dorsal pancreatic bud during embryogenesis resulting in agenesis of the neck, body and tail. It can present with hyperglycemia, abdominal pain, pancreatitis, or pancreatic tumors. To our knowledge, CES has never been reported to be associated with ADP, other pancreatic structural anomalies or pancreatitis. In addition, using US and CT, the diagnosis was missed as the absence of the body and tail in the setting of pancreatitis was interpreted as atrophy and fat replacement of the pancreatic tissue. MRCP with secretin provided an invaluable tool to allow further delineation of the pancreatic ductal and parenchymal anatomy without the risk of post-procedure pancreatitis from ERCP. Although we were unable to demonstrate pancreatic exocrine insufficiency, she had some improvement in her pain with pancreatic enzyme supplementation. Many patients with ADP also develop hyperglycemia presumably from loss of beta-islet cell mass. Due to the functional reserve of the endocrine and exocrine pancreas it is possible that these complications may arise with advancing age. We started our patient on an antioxidant cocktail (selenium, ascorbic acid, beta-carotene, α-tocopherol, methionine) to help prevent further free radical injury to the pancreas and help preserve the existing pancreatic tissue.

Serum levels of folate, lycopene, β-carotene, retinol and vitamin E and prostate cancer risk

Previous studies relating increased serum levels of folate and fat-soluble vitamins to prostate cancer risk have variously shown null associations or to either decrease or increase the risk of developing prostate cancer. Prospective studies of serum folate levels have been reported to show a null association and increased serum levels to either decrease or increase the risk of subsequently developing prostate cancer. Similarly, serum β-carotene and lycopene levels have either been reported to be inversely correlated or not associated with prostate cancer risk. Using a prospective nested case-control study design, which minimized the possibility of disease effects on serum-vitamin concentrations, we report null associations for serum concentrations of folate, lycopene, β-carotene, vitamin A and vitamin E, and subsequent development of prostate cancer.

The apolipoprotein A5 (APOA5) gene predisposes Caucasian children to elevated triglycerides and vitamin E (Four Provinces Study)

Objective Apolipoprotein A-V plays an important role in lipid metabolism regulation, particularly modulating triglyceride levels, as has been shown by many association studies in adults. The aim of this study was to analyse the effect of APOA5 on lipid profiles and fat-soluble vitamins (due to its strong relationship with triglyceride metabolism) in children. Methods We determined polymorphisms −1131T>C and S19W in the APOA5 gene in 964 6–8-year-old participants of the 4P study and analysed the influence of the APOA5 gene on plasma lipid levels (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides), apolipolipoproteins (apo A-I and apo B) and fat-soluble antioxidant vitamin (α-tocopherol, γ-tocopherol, lycopene, α-carotene, β-carotene and retinol) levels. Results The allele frequencies of both polymorphisms were comparable to those described in adult Caucasian populations (0.08 and 0.07 for −1131T>C and S19W, respectively). Boys carrying the −1131C allele have a 12% increase in circulating triglyceride levels ( p = 0.016) and a 7% decrease in HDL phospholipid levels ( p = 0.016). Linked to its effect on triglycerides, boys with the −1131C allele also have a 5% increase in plasma α-tocopherol levels ( p = 0.032). This effect was not observed in female participants. Boys carrying the rare allele for the S19W polymorphism have a 4% increase in circulating cholesterol levels ( p = 0.045), whereas girls have a 9% increase in circulating triglyceride levels ( p = 0.029). Linked to its effect on triglycerides, female carriers of the rare allele for S19W also have a 6% increase in α-tocopherol levels ( p = 0.009). Conclusion In children, the effect of APOA5 gene variants on triglyceride levels is related to gender, and because of the strong relationship between lipid metabolism and fat-soluble antioxidant vitamins, it also involves a significant elevation in α-tocopherol concentrations.

Total antioxidant capacity and lipid peroxidation in liver transplantation.

Liver transplantation is an accepted therapy for chronic liver disease patients. These patients generally have low levels of fat soluble vitamins, which have important antioxidant roles. Therefore, this study was undertaken to investigate whether such patients had evidence of antioxidant depletion and increased lipid peroxidation before transplant and whether the subsequent ischemia and reperfusion encountered during liver transplantation have any effect on antioxidant levels and lipid peroxidation. We assessed plasma total antioxidant capacity and serum lipid peroxide in 12 patients undergoing liver transplantation and equal numbers of healthy subjects. We found that before reperfusion, antioxidant levels were significantly decreased along with significantly elevated lipid peroxidation levels as compared with healthy controls (P<0.001). On reperfusion of the liver graft, further declined values of total antioxidant accompanied with highly elevated lipid peroxidation were seen than those of pre-reperfusion samples (P<0.001). This data shows that patients undergoing liver transplant have lowered antioxidant defenses and evidence of free radical damage, which compound the additional insult of reperfusion injury. Therefore antioxidant therapy in these patients before transplantation may ameliorate the effects of reperfusion.

Efficacy of plant sterols in novel matrices on blood lipid profiles: medium-chain triglycerides and low-fat products consumed with or without a meal

Cardiovascular disease (CVD) risk can be lowered by introduction of plant sterols (PSs) to the diet, since PSs have been shown to reduce low-density lipoprotein cholesterol (LDL-C). Given that the efficacy of PSs as cholesterol-lowering agents depends on their appropriate solubilization, the cholesterol-lowering efficacy of PSs in non-traditional matrices needs to be determined. The primary aim of this thesis was to examine the consumption of PSs (i) in an oil that is rich in medium-chain triglycerides (MCTs) or (ii) low-fat yogurt with or without a meal, on changes in lipid parameters. Additional objectives were to assess the effects of MCTs with PSs on body composition and energetics, to compare the effects of PSs in a low-fat matrix consumed with or without a meal on cholesterol synthesis, to evaluate the risks of PSs in a low-fat matrix on blood levels of carotenoids and fat-soluble vitamins, and to investigate the relationship between the response to PSs, cholesterol kinetics, and genotyping. For this purpose, two randomized, controlled, crossover feeding trials were conducted. First, 23 overweight, hyperlipidemic men consumed PSs in MCTs or an olive oil control for 6 weeks each. In the second trial, 26 hyperlipidemic subjects consumed a placebo yogurt, a PS-enriched yogurt consumed with a meal, or afternoon PS-enriched yogurt as a snack for 4 weeks each. PSs, mixed within an MCT matrix, lowers plasma total cholesterol (TC) and LDL-C without changing the high-density lipoprotein cholesterol concentrations. However, no changes in body composition or energetics were observed. Second, a PS-enriched low-fat yogurt as a snack lowered TC, along with a lowering trend in LDL-C, to a greater extent than when consumed with a meal without any risk of deficiency in fat-soluble antioxidants. An increase in cholesterol biosynthesis was also observed in both PS phases compared with the control phase. In addition, 3 subjects who were non-responsive to PS intervention and had higher cholesterol absorption rates were observed; however, no recognizable pattern of genetic polymorphism was detected. Overall, these novel matrices for PS incorporation consumed with or between meals may be an effective way of decreasing the risk of CVD; however, some individuals respond better to PS intervention.

Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency

Our aim was to characterize HDL subspecies and fat-soluble vitamin levels in a kindred with familial apolipoprotein A-I (apoA-I) deficiency. Sequencing of the APOA1 gene revealed a nonsense mutation at codon -2, Q[-2]X, with two documented homozygotes, eight heterozygotes, and two normal subjects in the kindred. Homozygotes presented markedly decreased HDL cholesterol levels, undetectable plasma apoA-1, tuboeruptive and planar xanthomas, mild corneal arcus and opacification, and severe premature coronary artery disease. In both homozygotes, analysis of HDL particles by two-dimensional gel electrophoresis revealed undetectable apoA-I, decreased amounts of small alpha-3 migrating apoA-II particles, and only modestly decreased normal amounts of slow alpha migrating apoA-IV- and apoE-containing HDL, while in the eight heterozygotes, there was loss of large alpha-1 HDL particles. There were no significant decreases in plasma fat-soluble vitamin levels noted in either homozygotes or heterozygotes compared with normal control subjects. Our data indicate that isolated apoA-I deficiency results in marked HDL deficiency with very low apoA-II alpha-3 HDL particles, modest reductions in the separate and distinct plasma apoA-IV and apoE HDL particles, tuboeruptive xanthomas, premature coronary atherosclerosis, and no evidence of fat malabsorption.

Novel mutations in abetalipoproteinaemia and homozygous familial hypobetalipoproteinaemia

Abetalipoproteinaemia (ABL) and homozygous familial hypobetalipoproteinaemia (FHBL) are rare inherited disorders associated with low or undetectable levels of apolipoprotein B (apoB)-containing lipoproteins. Patients present with the symptoms and sequelae of fat malabsorption, including fat-soluble vitamin deficiencies. We describe two novel mutations: one an APOB gene mutation causing FHBL and the other a microsomal triglyceride transfer protein (MTP) gene mutation causing ABL. Two siblings of consanguineous parents were homozygous for an apoB mutation 4339delT causing an apoB-30.9 truncation. In another family, a boy born to consanguineous parents was homozygous for a 319 bp in-frame deletion of MTP exon 15 (c.2076-39_2303 + 52del319). All three children presented with malabsorption and liver dysfunction and had similar very low serum lipid, apoB, and fat-soluble vitamin levels. The FHBL parents had low serum lipid and apoB profiles distinguishing the disorder from the normal levels in ABL parents. Future patients presenting with FHBL or ABL should be genotyped to provide further insight into the varying clinical severity related to molecular heterogenicity in these two conditions.

Status of methodology for the determination of fat-soluble vitamins in foods, dietary supplements, and vitamin premixes.

Fat-soluble vitamins (FSVs) include vitamin A, carotenoids, vitamins D, E, and K. New legislation is being introduced in many countries to reinforce regulatory compliance of declared concentrations of vitamins and other micronutrients in food products and dietary supplements. The levels of FSVs are likely to be more closely scrutinized due to their potential health risks associated with overdosing, in particular of vitamin D. However, a proviso of stricter regulatory compliance is that analytical methods must be fit-for-purpose, providing adequate accuracy and precision. Official methods have been published by organizations such as AOAC INTERNATIONAL, European Committee for Standardization, International Dairy Federation, U.S. Pharmacopeia, and International Organization for Standardization. The methods available for foods, dietary supplements, and vitamin premixes are evaluated in this review. In general, these methods show adequate precision for regulatory compliance; however, the field of application has not often been evaluated for a sufficiently large range of food matrixes. Gaps have been noted in the range of published official procedures, particularly for carotenoids and vitamin premixes. The potential of some recent developments in sample preparation and chromatographic techniques were evaluated to provide improved procedures for FSV analysis the future.

Fish-oil esters of plant sterols differ from vegetable-oil sterol esters in triglycerides lowering, carotenoid bioavailability and impact on plasminogen activator inhibitor-1 (PAI-1) concentrations in hypercholesterolemic subjects

BackgroundConsumption of plant sterol (PS) esters lower low-density lipoprotein (LDL)-cholesterol levels by suppressing intestinal absorption of cholesterol. Commercially available PS are mainly esterified to omega-6 fatty acid (FA), such as sunflower oil (SO) FA. Emerging trends include using other sources such as olive oil (OO) or omega-3 FA from fish oil (FO), known to exert potent hypotriglyceridemic effects. Our objective was to compare the actions of different FA esterified to PS on blood lipids, carotenoid bioavailability as well as inflammatory and coagulation markers.MethodsTwenty-one moderately overweight, hypercholesterolemic subjects consumed experimental isoenergetic diets enriched with OO (70% of fat), each lasting 28-day and separated by 4-week washout periods, using a randomized crossover design. Diets were supplemented with three PS esters preparations, PS-FO, PS-SO, or PS-OO. All PS treatments contained an equivalent of 1.7 PS g/d, and the PS-FO provided a total of 5.4 g/d FO FA (eicosapentaenoic and docosahexaenoic acids).ResultsThere were no differences between PS-containing diet effects on total cholesterol, LDL-cholesterol, or high-density lipoprotein (HDL)-cholesterol levels. However, PS-FO consumption resulted in markedly lower (P < 0.0001) fasting and postprandial triglyceride concentrations compared with PS-SO and PS-OO. These treatments affected plasma β-carotene (P = 0.0169) and retinol (P = 0.0244), but not tocopherol (P = 0.2108) concentrations. Consumption of PS-FO resulted in higher β-carotene (P = 0.0139) and retinol (P = 0.0425) levels than PS-SO and PS-OO, respectively. Plasma TNF-α, IL-6, C-reactive protein, prostate specific antigen, and fibrinogen concentrations were unaffected by the PS-interventions. In contrast, plasminogen activator inhibitor 1 (PAI-1) concentrations were lower (P = 0.0282) in the PS-FO-fed than the PS-SO, but not the PS-OO (P = 0.7487) groups.ConclusionOur findings suggest that, in hypercholesterolemic subjects consuming an OO-based diet, PS-FO results in lowered blood triglyceride and PAI-1 concentrations, and higher fat-soluble vitamin levels in comparison to the vegetable oil FA esters of PS (PS-SO and PS-OO). Thus, PS-FO may offer hyperlipidemic subjects a more comprehensive lipid lowering approach while reducing the potential risk of decreased plasma carotenoid concentrations.

Dietary Intake, Neutrophil Fatty Acid Profile, Serum Antioxidant Vitamins and Oxygen Radical Absorbance Capacity in Patients with Ulcerative Colitis

Nutrition may play an important role in the pathogenesis and treatment of ulcerative colitis. Several studies suggest an association between dietary factors and the onset of ulcerative colitis; however, only few studies have examined the relationship between dietary intake and relapse of ulcerative colitis. The aim of this study was to assess the dietary intake and antioxidative capacity of ulcerative colitis patients and to elucidate the efficacy of dietary therapy for ulcerative colitis. Dietary intake, fatty acid composition of phospholipids in plasma and neutrophils, serum fat-soluble vitamin levels, and oxygen radical absorbance capacity were analyzed in 29 ulcerative colitis patients (7 males and 22 females), who were treated at the Department of Gastroenterology, Okayama University Hospital. Total fat intake, fat energy ratio and linoleic acid intake were significantly lower, while protein and carbohydrate intakes were significantly higher, in the patients than age- and sex-matched controls. In the neutrophil phospholipids of ulcerative colitis patients, significantly higher levels of linoleic aicd and arachidonic acid and a lower level of eicosapentaenoic acid were observed. The concentrations of serum retinol and beta-carotene but not alpha-tocopherol were significantly lower and serum oxygen radical absorbance capacity was also lower than in the controls. Significant correlations between serum oxygen radical absorbance capacity and retinol (r = 0.567, p = 0.0031), alpha-tocopherol (r = 0.560, p = 0.0036) and beta-carotene (r = 0.440, p = 0.0279) concentrations were observed in the ulcerative colitis patients. A diet restricting the intake of linoleic acid and supplemented with eicosapentaenoic acid and antioxidative vitamins may be recommendable for the nutritional management of ulcerative colitis patients.

Anemia in Cystic Fibrosis (CF): Prevalence, Mechanisms and Correlation with Pulmonary Function.

CF is a chronic disease associated with inflammation and an unknown prevalence of anemia. In other settings anemia is associated with increased morbidity and mortality, and recognition and correction of anemia in CF patients might lead to better outcomes. We hypothesized that chronic inflammation (ACI), iron deficiency (IDA) and malabsorption may be important mechanisms contributing to the anemia in CF patients.METHODS: Clinical charts and portCF.org visit logs of 218 patients of all ages (1 m to 61 yrs) with CF were reviewed for as many years as charts permitted (range 1–7 yrs). The following data were extracted: CBC, iron studies, pulmonary function tests (PFTs), vitamins A, D, and E levels, creatinine, pertinent medical history, and current medications. Anemia was defined by age- and gender-specific WHO criteria. Patients were considered anemic if low Hb was present on two separate occasions at least two months apart, or average annual Hb met WHO criteria. PFTs in 176 patients (all >6 yrs) included forced expiratory volume (FEV1) and forced vital capacity (FVC) as percent predicted of normal and were considered a reflection of patient performance. The most representative annual PFT from at least 4 annual tests was chosen for analysis since acute infection adversely influences daily performance. Semiannual vitamin levels of 47 adults were correlated with corresponding Hb values.RESULTS: 61 of 218 patients, ages 1 m to 61 yrs, were anemic (prevalence 28%). The percent of anemia in different age groups varied. Children <11yrs had a prevalence of anemia of 18.5% while adolescents had a prevalence of only 4%. Of 111 adults >18 yrs, 48 were anemic (43%) with a progressive age-related increase in the prevalence of anemia reaching 58% in patients >40 yrs. Complete iron studies were available in 16/48 patients. 7 were identified as IDA, 4 as ACI, and 3 as combined; 2 others had renal failure. In 32 patients, iron studies were incomplete, but renal failure, hemoptysis, hematochezia and solid organ transplants were contributing factors in half. PFTs obtained in 176 patients >7 yrs were compared in anemic and non-anemic patients. Mean FEV1 and FVC at all ages were statistically significantly poorer in the anemic patients (p <0.005). There was no correlation between vitamin levels and Hb. Complete iron studies were also available in 9 non-anemic patients with impaired lung function. 8/9 patients had ferritins <35 ng/ml. Transferrin saturation was <18% in 7 and 21% and 23% in the remaining 2, suggesting relative iron deficiency.CONCLUSIONS: The prevalence of anemia in CF patients is high and increases with age. In patients for whom iron studies were available, IDA was the prominent underlying mechanism, followed by ACI or a combination of both. There was no correlation between fat soluble vitamin levels and Hb, indicating malabsorption is not a major contributor to the anemia. There was a strikingly significant association between anemia and poor pulmonary function in all age groups. In addition, a group of non-anemic patients with poor lung function had relative iron deficiency. Our results indicate that iron deficiency in anemic CF patients, as well as relative iron deficiency in non-anemic CF patients might be underrecognized and undertreated. Since anemia is associated with poor pulmonary function, correction of anemia should be attempted. Identification of relative iron-deficient states in non- or borderline anemic CF patients with poor lung function could be important since iron supplementation might allow Hb levels to increase as an appropriate response to hypoxia.

Serum Retinol, α-Tocopherol, and β-Carotene Levels Are Not Altered by Excess Ingestion of Diacylglycerol-Containing Plant Sterol Esters

Background: Diacylglycerol (DAG) suppresses the postprandial increase in serum triglycerides, and has antiobesity effects. On the other hand, plant sterol esters (PSE) lower serum cholesterol levels in hypercholesterolemia. Thus, DAG-containing PSE (PSE/DAG) would be expected to maintain an appropriate serum cholesterol level and decrease the risk of arteriosclerotic disorders. Several recent studies, however, report negative effects of PSE on serum fat-soluble (pro)vitamin levels. The objective of this study was to investigate the effect of PSE/DAG on serum retinol, β-carotene, and α-tocopherol levels using a threefold excess of the effective dose obtained in our previous study. Methods: A randomized placebo-controlled double-blind parallel study was performed in healthy and mildly hypercholesterolemic subjects, in which the subjects ingested 1.2 g PSE/30 g DAG for 2 weeks in the form of mayonnaise-type products. Triacylglycerol (TAG) mayonnaise was used as a control. Result: There were no subjective adverse effects or changes in serum retinol, α-tocopherol, and β-carotene levels, abdominal symptoms, hematologic values, or blood biochemical values. Conclusion: Ingestion of a threefold excess of PSE/DAG for 2 weeks had no adverse effects compared to ingestion of conventional TAG mayonnaise.

Hydrophilic formulation of lipophilic vitamins and carotenoids with excellent bioavailability in patients with cystic fibrosis

Patients with cystic fibrosis (CF) show distinct vitamin deficits and elevated indicators of oxidative stress. We estimated fat soluble vitamins and carotenoids and protein carbonyls and TBARS in plasma and buccal mucosa (BM) of 22 patients with CF and 35 healthy controls. In patients with CF plasma and BM levels of fat soluble vitamins and carotenoids were significantly lower and markers of oxidative stress significantly higher compared to healthy volunteers. A subgroup Adult CF patients showed the lowest vitamin level and the highest indicators of oxidative stress. The major reason is the increasing fat malabsorption with the consequence a low absorption of fat soluble vitamins and carotenoids in these patients. To improve the absorption we tested a special “water soluble” formulation of vitamin A, E and β-carotene versus a conventional formulation in a clinical intervention trial (RCT) in 34 CF patients over a time period of 6 month. Plasma levels of vitamin A, E and β-carotene increased in the group treated with the micellised formulation, whereas in the group with the conventional formulation the levels remained either constant or tended to decrease. β-carotene increased significant in BM in the group with micellised formulation. Specifically the increase in plasma vitamin A documents that the patients suffered from a vitamin A deficiency despite plasma levels in a normal range. Despite nearly normal plasma levels of vitamin E and β-carotene the concentration of these compounds was very low in buccal mucosa cells prior supplementation compared to healthy volunteers. The new formulation offers a new and successful approach to supply fat soluble compounds in patients with fat malabsorption.

Safety aspects and cholesterol-lowering efficacy of low fat dairy products containing plant sterols

The aim of this study was to investigate whether a plant sterol mixture would reduce serum cholesterol when added to low fat dairy products in subjects with hypercholesterolaemia, and to examine the effects of the mixture on the serum plant sterol and fat-soluble vitamin levels. A parallel, double-blind study. The study was performed in three different locations in Finland. In total, 164 mildly or moderately hypercholesterolaemic subjects participated in the study. The subjects were randomly divided into two groups: a plant sterol group and a control group. The subjects consumed the products for 6 weeks after a 3-week run-in period. The targeted plant sterol intake was 2 g/day in the sterol group. During the treatment period, there was a 6.5% reduction in serum total cholesterol in the sterol group while no change was observed in the control group (P<0.0005). Serum low-density lipoprotein (LDL) cholesterol was reduced by 10.4% in the sterol group and by 0.6% in the control group (P<0.00005). There was no change during the trial in serum high-density lipoprotein (HDL) cholesterol or triacylglycerol concentrations. The HDL/LDL cholesterol ratio increased by 16.1% in the sterol group and by 4.3% in the control group (P=0.0001). Serum plant sterol levels increased significantly (P=0.0001) in the sterol group. None of the fat-soluble vitamin levels decreased significantly when changes in serum total cholesterol were taken into account. The hypocholesterolaemic effect of sterol administration was not influenced by apolipoprotein E phenotype. Yoghurt, low-fat hard cheese and low-fat fresh cheese enriched with a plant sterol mixture reduced serum cholesterol in hypercholesterolaemic subjects and no adverse effects were noted in the dietary control of hypercholesterolaemia.

Treatment options for chronic cholestasis in infancy and childhood

Altered bile flow physiology leads to many complications commonly seen in patients with cholestatic liver disease, regardless of the etiology. For each individual patient, a coordinated and effective treatment strategy must address the presence and the severity spectrum of malabsorption, malnutrition, vitamin and micronutrient deficiencies, pruritus, xanthomata, ascites, and liver failure, which are attributed directly or indirectly to diminished bile flow. An aggressive approach to maximizing the nutritional status of the child is vital to ensure optimal growth and development. Protein-calorie and/or fat supplementation is best discussed early. Decreasing the percentage of dietary long-chain triglycerides, providing medium-chain triglycerides, and ensuring adequate essential fatty acid and adequate protein intake may be helpful. Fat-soluble vitamin (A, D, E, and K) levels and micronutrient levels must be carefully and serially monitored and supplemented as necessary. Because the mechanisms that mediate pruritus of cholestasis remain to be determined, the use of empirical therapies continues to be standard practice. Ursodeoxycholic acid may ameliorate pruritus. Antihistamines and rifampicin may also provide temporary relief for some children. Based on the evidence that increased central opioidergic tone is present in chronic cholestasis, the use of opiate antagonists is promising but has not been evaluated in children. Selected patients with refractory pruritus that have failed maximal medical therapy have benefited from partial external biliary diversion. Ongoing dialogue with the family regarding the indications for liver transplantation is reasonable. Optimization and adherence with the pretransplant medical management enhance the chances for a successful outcome from liver transplantation. Specific to the pediatric patient, optimizing growth, development and nutrition, minimizing discomfort and disability, and aiding the child and family in coping with the stress, social, and emotional effects of chronic liver disease remain paramount.

CFTR Mutations

Acute pancreatitis (AP) is a rare association with Campylobacter jejuni (C. jejuni) enteritis. AP in association with another infectious illness like enteritis, may be related to an underlying genetic mutation. We report a patient with C. jejuni and AP, who was later found to have cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. A 15 yr old girl presented with abdominal pain and non bloody diarrhea for 8 days. She had a 5 lb weight loss, bilateral knee pain, 103.8°C fever and had used acetaminophen and ibuprofen. Past history was significant for poor growth, recurrent abdominal pain, and serum lipase elevated two fold normal on two occasions. Other tests in the past were a normal ultrasound and CT of abdomen, upper gastrointestinal and small bowel series, HIDA scan, celiac disease serology and duodenal biopsies. Sweat chloride test showed Na of 69 and Cl of 60 (N 0–40 mEq/L); pulmonary function tests, 72-h fecal fat, and fat soluble vitamin levels were normal. Family history revealed celiac disease in a cousin. She had unpasteurized milk 1 week prior to the acute illness. On admission her weight was <3% ile and exam revealed epigastric tenderness. Pertinent investigations were serum amylase of 103 (N < 90 IU/L) and lipase of 3,663 (N < 200 IU/L). Pain was managed with meperidine, feedings were held and intravenous fluids were started. Fasting lipid panel, repeat abdominal ultrasound and CT were normal. C. jejuni was detected on stool culture and she was treated with azithromycin for 7 days. She was pain free while she received nasojejunal nutrition with Ensure but notably serum amylase and lipase peaked to 554 & 21,047 respectively. Magnetic resonance cholangiopancreatography at this stage was normal. Furthermore, a buccal swab was performed for CF genetic mutation analysis; she was a compound heterozygote for R 117H, Δ F508 mutations. At 1 month follow-up, she remained asymptomatic on a regular diet and, serum amylase & lipase decreased to 308 & 650 respectively. CFTR mutations predispose to recurrent acute & chronic pancreatitis. In our patient with genetic predisposition to AP due to CFTR mutations, C. jejuni was thought to be an environmental modifier in initiating the acute episode.

Decrease in plasma low-density lipoprotein cholesterol, apolipoprotein B, cholesteryl ester transfer protein, and oxidized low-density lipoprotein by plant stanol ester-containing spread:: A randomized, placebo-controlled trial

Objective The ester of plant stanols significantly reduces plasma levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in Western people. Effects of plant stanol ester-containing spread on plasma levels of TC, LDL-C, and apolipoprotein B (apoB) were studied in a randomized, placebo-controlled trial in Japanese subjects whose diet is low in fat and cholesterol. The effects of plant stanol ester on plasma levels of arteriosclerosis-promoting factors, namely remnants of triacylglycerol (TG)-rich lipoproteins, cholesteryl ester transfer protein (CETP), and oxidized LDL (Ox-LDL), were also studied. The assessment of safety was also made. Methods One hundred five healthy volunteers were assigned randomly to one of three groups: placebo spread ( n = 35), 2 g/d of plant stanol (3.4 g of stanol ester; n = 34), and 3 g/d of plant stanol (5.1 g of stanol ester; n = 36). Plasma levels of lipids were measured at start of the study, at 2 and 4 wk (end of trial), and at 8 wk (+4 wk). Plasma apoproteins, cholesterol in remnant-like particles which are equivalent to remnants of TG-rich lipoproteins (RLP-C), CETP mass, and Ox-LDL were measured at the beginning and the end of the trial. Plasma levels of plant steroids and fat-soluble vitamins were also measured for the assessment of safety. Results Background and dietary composition did not differ among groups. Plasma levels of TC, LDL-C, apoB, apoE, CETP mass, and Ox-LDL were reduced significantly by 6.5%, 9.6%, 8.3%, 4.5%, 6.1%, and 20%, respectively, in the 2 g/d plant stanol group. Plasma levels of TC, LDL-C, apoB, CETP mass, and Ox-LDL were decreased significantly by 5.5%, 7.3%, 5.6%, 3.3%, and 19%, respectively, in the 3 g/d plant stanol group. Plasma levels of plant stanols, plant sterols, retinol, β-carotene, and α-tocopherol did not change in any group, but levels of campestanol increased and α-tocopherol decreased slightly in the sitostanol groups. Conclusion Plasma levels of TC and LDL-C were significantly reduced by the plant stanol ester-containing spread. The smaller reduction than in Western studies and the lack of dose dependency in this study might be due to the different basal diets. We concluded that plant stanol ester-containing spread is efficacious in reducing plasma LDL-C, apoB, CETP, and Ox-LDL and that 2 g/d plant stanol is adequate for Japanese people. No significant side effects were observed in any group.

Recognizing and diagnosing pancreatic insufficiency in infants.

1. Peter Francis Belamarich, MD 1. Einstein College of Medicine-Children’s Hospital at Montefiore Bronx, NY 1. Exocrine Pancreatic Dysfunction. Cystic Fibrosis. Gaskin K. In: Walker WA, Durie PR, Hamilton JR, Walker-Smith JA, Watkins JB, eds.Pediatric Gastrointestinal Disease, Hamilton, Ontario, Canada: BC Decker Inc;.2000;:1353–1369 2. Pancreatic Function Tests. Huynh H, Couper R. In: Walker WA, Durie PR, Hamilton JR, Walker-Smith JA, Watkins JB, eds.Pediatric Gastrointestinal Disease, Hamilton, Ontario, Canada: BC Decker Inc.2000;:1515–1528 3. Hereditary and Childhood Disorders of the Pancreas. Lopez MJ, Grand RJ. In: Feldman MH, Sleisenger MH, Scharschmidt BF, eds.Sleisenger and Fordtran’s Gastrointestinal and Liver Disease Philadelphia, Pa: WB Saunders.1998;:782–808 Pancreatic insufficiency (PI) is uncommon among infants, but it is important to recognize. Early diagnosis followed by oral enzyme replacement therapy can avert the significant morbidity that follows upon severe malnutrition in infancy. In addition, for the majority of infants who have PI and subsequently are found to have cystic fibrosis, early diagnosis allows genetic counseling to be offered and can help prevent progression of associated pulmonary disease. The pathophysiology of pancreatic insufficiency is complex. Malabsorption results from inadequate secretion of the approximately 20 enzymes and cofactors derived from the pancreatic acini as well as from insufficient bicarbonate secretion from the ductal epithelium. Without adequate bicarbonate to neutralize gastric acid, whatever limited pancreatic lipase is available cannot function optimally, and bile salt micellization of dietary fat droplets also is impaired. Thus, fat digestion takes a “double hit,” and fat malabsorption becomes a prominent clinical feature of PI. Protein maldigestion and malabsorption are also substantial, but they are more commonly subclinical. Quantitative studies of pancreatic enzyme secretion have shown that the pancreas has a tremendous functional reserve. Significant fat malabsorption does not occur until lipase secretion is below 2% of normal values. Thus, clinically apparent PI represents not mild or …