Malabsorption Of Vitamin Research Articles

Parathyroid Hormone and Bone Marker Levels in Patients with Morbid Obesity Before and After Biliopancreatic Diversion

Scopinaro biliopancreatic diversion (BPD) is associated with malabsorption of calcium and vitamin D, which manifests as a secondary hyperparathyroidism (SHP) and may lead to osteopenia. 96 morbidly obese patients were studied (age 19-60 years, 23 men and 73 women, with mean initial BMI 53) following intervention by Scopinaro BPD. The change in iPTH levels, urine DPD, Pyrilinks-D of DPC and serum CTx were studied at 0, 3, 6, 12, 18 and 24 months after surgery. Postoperatively, they were given supplements of calcium and vitamin D3. The control group consisted of 67 non-obese women and 10 men. The iPTH levels gradually increased after BPD, with a substantial difference compared to presurgery levels at month 6. In spite of the calcium and vitamin D supplements, 77% of the patients with presurgery SHP did maintain high levels of iPTH after 2 years. The percentage of SHP among the patients with normal pre-surgery iPTH was 58%. The basal figures of DPD/cre were significantly higher than in the control group, 9.06 (4.6-13.5) nM/mMcre vs 3.9 (2.8-5.6) in men and 6.75 (5.4-7.9) vs 7.67 (3.3-11.6) in women, but not CTx, 0.24 (0.02-0.89) vs 0.22 (0.07-0.55). After the operation, there was a noticeable increase which persisted at 2 years. There was a lack of correlation between the levels of iPTH and the bone resorption markers, i.e. the first ones decreased from month 6 in men and from month 12 in women, while the levels of iPTH continued to increase. In obese patients, we found no correlation between iPTH levels and BMI. Supplements of calcium and vitamin D did not prevent the appearance of SHP following BPD. The patients with high pre-surgery iPTH levels have a higher risk of malabsorption of calcium and vitamin D. Following malabsorptive bariatric surgery, there is an increase in bone resorption, which results in DPD and CTx increase. Those markers do not correlate with iPTH, and this may suggest that there is a phenomenon of bone reshaping parallel to the loss of weight.

HEPATIC AND INTESTINAL CHANGES IN RATS TREATED WITH T-0126, A MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN (MTP) INHIBITOR

In the present study, we investigated the potential toxic effects of 2-week oral treatment with T-0126, a novel microsomal triglyceride transfer protein (MTP) inhibitor, on the liver and intestine in male and female rats. Administration of T-0126 decreased serum lipids and resulted in fat accumulation in the liver and the small intestine. In addition, slight changes in the liver, including an increase in serum aminotransferase (AST and ALT) activity, presence of focal inflammatory lesions, and prolongation of PT and APTT were observed after treatment with T-0126. These changes may be related to a mechanism based on malabsorption of fat, fat-soluble antioxidants, and vitamin K, although we cannot exclude other potential mechanisms such as direct cytotoxicity of T-0126.

Update on maintaining bone health in cystic fibrosis

The high prevalence of decreased bone density in adults with cystic fibrosis is now well recognized, and guidelines for screening and treatment of cystic fibrosis-related bone disease have recently been published. This review summarizes the current best practices for optimizing bone health in cystic fibrosis and highlight recent findings that provide insight into the etiology of cystic fibrosis-related bone disease. Recent research suggests that cystic fibrosis-related bone disease actually starts during childhood, when individuals with cystic fibrosis fail to demonstrate normal bone calcium accretion. The failure to reach peak bone mass is made worse by increased osteoclast activity and bone resorption. This combination results in decreased bone density and an increased risk of fracture. Recent clinical studies suggest that multiple contributing factors need to be addressed in cystic fibrosis to optimize bone health: malnutrition, vitamin and mineral malabsorption, recurrent infections, inadequate sex hormones, and lack of exercise. Oral bisphosphonates have been demonstrated to be effective in cystic fibrosis and should be used when osteoporosis or progressive osteopenia is present. Research suggests cystic fibrosis-related bone disease actually begins during childhood, and guidelines now exist to aid in identifying and treating those with decreased bone density.

ELEVATED SERUM RETINOL LEVELS IN CHILDREN AND YOUNG ADULTS WITH CYSTIC FIBROSIS

Background: Cystic fibrosis (CF) and pancreatic insufficiency (PI) predispose patients to fat and fat-soluble vitamin malabsorption despite pancreatic enzyme replacement. Recent evidence suggests current patterns of vitamin A supplementation may be excessive. Aims: To assess serum retinol and vitamin A intake in children and young adults with CF and PI compared to healthy subjects. Methods: Participants, 8 to 25 years old, had blood collected, growth status (height [HAZ] and weight [WAZ] Z scores) and FEV1 (% predicted) assessed. Serum retinol (μg/dL) was analyzed by HPLC and compared with age-matched reference ranges (5th and 95th %iles) for non-Hispanic white subjects from NHANES 1999-2002. Vitamin A intake (food and supplement-based, pre-formed retinol and total vitamin A) was reported in retinol activity equivalents (μg RAE) from 3-day weighed food records. Vitamin A intake was compared with Dietary Reference Intakes (DRI) and with CF recommendations. Results: Serum retinol, growth status and FEV1were available for 78 subjects and dietary intake data for 53 subjects. 42% of subjects had serum retinol within, and 58% above the reference range (30 to 72 μg/dL). Total vitamin A intake (mean ± sd; μg RAE/d) was 608 ± 431% of the Recommended Dietary Intake (RDA); 67% from supplements. Preformed retinol intake was 564 ± 409 %RDA. 86% of subjects had total preformed retinol intake above the DRI Tolerable Upper Limit of Intake, and 73% above CF recommendations. Serum retinol was inversely correlated with HAZ and WAZ (r = −0.28 for both, P < 0.05), but not associated with FEV1, age or gender. Conclusions: Elevated serum retinol levels and excessive preformed vitamin A intake raise concerns regarding the use, dose, and formulation (preformed, water miscible) of vitamin A supplements in CF care. The possibility of and risk for vitamin A toxicity require further study. Supported by R01 HL57448, GCRC (5-M01-RR00240), and Nutrition Center at CHOP, and the CF Foundation.

Defects in Bile Acid Biosynthesis‐Diagnosis and Treatment

Bile acid synthetic defects represent a specific category of metabolic liver disease. This article highlights the history and summarizes our analytical approach to the diagnosis and treatment of genetic defects in bile acid synthesis. By the application of mass spectrometry as a screening tool, it is possible to perform rapid diagnosis of potential inborn errors in bile acid synthesis from urinary bile acid analysis. Molecular techniques then afford the identification of specific mutations in genes encoding the enzymes responsible for bile acid synthesis. Using this approach, 6 of the 7 known genetic defects that are causes of progressive cholestatic liver disease, syndromes of fat-soluble vitamin malabsorption, or neurological disease, have been characterized. Bile-acid therapy using oral cholic acid has proven effective in most of these bile acid synthetic defects making early diagnosis crucial to optimum clinical prognosis.

Leber’s hereditary optic neuropathy and vitamin B12 deficiency

Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. A case series was observed. Three patients who developed bilateral optic neuropathy are presented. All patients had a primary LHON mutation in their mtDNA, but also a subnormal vitamin B12 serum level at the time of presentation. The clinical picture of optic neuropathy associated with vitamin B12 deficiency shows similarity to that of LHON. Both involve the nerve fibres of the papillomacular bundle. The present case reports suggest that optic neuropathy in patients carrying a primary LHON mtDNA mutation may be precipitated by vitamin B12 deficiency. Therefore, known carriers should take care to have an adequate dietary intake of vitamin B12 and malabsorption syndromes like those occurring in familial pernicious anaemia or after gastric surgery should be excluded.

Celiac disease.

Celiac disease is a chronic intestinal disease caused by intolerance to gluten. It is characterized by immune-mediated enteropathy, associated with maldigestion and malabsorption of most nutrients and vitamins. In predisposed individuals, the ingestion of gluten-containing food such as wheat and rye induces a flat jejunal mucosa with infiltration of lymphocytes. The main symptoms are: stomach pain, gas, and bloating, diarrhea, weight loss, anemia, edema, bone or joint pain. Prevalence for clinically overt celiac disease varies from 1:270 in Finland to 1:5000 in North America. Since celiac disease can be asymptomatic, most subjects are not diagnosed or they can present with atypical symptoms. Furthermore, severe inflammation of the small bowel can be present without any gastrointestinal symptoms. The diagnosis should be made early since celiac disease causes growth retardation in untreated children and atypical symptoms like infertility or neurological symptoms. Diagnosis requires endoscopy with jejunal biopsy. In addition, tissue-transglutaminase antibodies are important to confirm the diagnosis since there are other diseases which can mimic celiac disease. The exact cause of celiac disease is unknown but is thought to be primarily immune mediated (tissue-transglutaminase autoantigen); often the disease is inherited. Management consists in life long withdrawal of dietary gluten, which leads to significant clinical and histological improvement. However, complete normalization of histology can take years.

Glucagon-Like Peptide-2: Update of the Recent Clinical Trials

Although long-term parenteral nutrition is lifesaving in patients with intestinal failure, it is expensive and associated with serious complications such as catheter sepsis, venous occlusions, and liver failure and severely impairs the quality of life in the short bowel patients. Therefore, treatments that increase the absolute intestinal absorption, thereby eliminating or minimizing the need for parenteral support, are needed. In this respect, glucagon-like peptide 2 (GLP-2) has received attention. In this review, the nature of the short bowel syndrome is described, and the antisecretory, transit-modulating, but also intestinotrophic effects of GLP-2 are presented. As illustrated in 2 pilot studies, one using native GLP-2 and the other a degradation-resistant analogue, teduglutide, these new agents may prove important in optimizing remnant intestinal function, thereby eliminating the need for parenteral support and improving quality of life in short bowel patients with intestinal failure.

Gut hormones, and short bowel syndrome: The enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation

Short bowel syndrome (SBS) refers to the malabsorption of nutrients, water, and essential vitamins as a result of disease or surgical removal of parts of the small intestine. The most common reasons for removing part of the small intestine are due to surgical intervention for the treatment of either Crohn's disease or necrotizing enterocolitis. Intestinal adaptation following resection may take weeks to months to be achieved, thus nutritional support requires a variety of therapeutic measures, which include parenteral nutrition. Improper nutrition management can leave the SBS patient malnourished and/or dehydrated, which can be life threatening. The development of therapeutic strategies that reduce both the complications and medical costs associated with SBS/long-term parenteral nutrition while enhancing the intestinal adaptive response would be valuable. Currently, therapeutic options available for the treatment of SBS are limited. There are many potential stimulators of intestinal adaptation including peptide hormones, growth factors, and neuronally-derived components. Glucagon-like peptide-2 (GLP-2) is one potential treatment for gastrointestinal disorders associated with insufficient mucosal function. A significant body of evidence demonstrates that GLP-2 is a trophic hormone that plays an important role in controlling intestinal adaptation. Recent data from clinical trials demonstrate that GLP-2 is safe, well-tolerated, and promotes intestinal growth in SBS patients. However, the mechanism of action and the localization of the glucagon-like peptide-2 receptor (GLP-2R) remains an enigma. This review summarizes the role of a number of mucosal-derived factors that might be involved with intestinal adaptation processes; however, this discussion primarily examines the physiology, mechanism of action, and utility of GLP-2 in the regulation of intestinal mucosal growth.

Risk for Osteoporosis and Antiresorptive Therapies in Patients with Crohn's Disease

Background: The risk of osteoporosis is greater in patients with inflammatory bowel disease (IBD) because of several related risk factors such as the prolonged use of corticosteroids, the malabsorption of calcium and vitamin D following small-bowel disease or small-bowel resections, and the inflammatory process resulting from the illness. A reduction in bone mineral density (BMD) has been reported in 30–75% of patients with IBD (Crohn's disease or ulcerative colitis). An evaluation of the risk factors of osteoporosis should be performed to identify those in need of antiresorptive drug therapies (ART) and/or calcium and vitamin D supplements. Objective: To determine whether patients with Crohn's disease at risk for osteoporosis or already having decreased BMD were identified as such and treated with appropriate therapy. Methods: A cross-sectional study was performed among 54 white patients with Crohn's disease who attended a gastroenterology specialized clinic between January and March 2002. All patients with Crohn's disease having an outpatient medical visit were asked to participate in the study. Patients who agreed to the study were questioned for Crohn's disease activity index (CDAI) and osteoporosis risk factors such as nutrition, lifestyle, and corticosteroid therapy. Serum bone-specific markers and nutritional status were assessed. BMD test of the lumbar vertebrae (L2–L4) and the nondominant hip were assessed with dual-energy X-ray absorptiometry if the participants did not have a BMD test in the year prior to the study. ART and calcium/vitamin D use were assessed through a questionnaire and on community pharmaceutical drug services in the 2 year period prior to the evaluation. Results: Mean age and CDAI severity score were 41.5 years and 145, respectively. None of the patients was evaluated for BMD in the year prior to the study. Osteopenia at the nondominant hip and/or lumbar vertebrae was seen in 29 patients. Eighty-two percent of patients with a T score under −2 SD had not been exposed to ART; 84% of patients with more than 4 risk factors for osteoporosis and a T score less than −1.5 SD had not received ART. Moreover, 88% of patients with a T score less than −1.5 SD and receiving corticosteroid therapy had not been treated with ART. Conclusions: The presence of osteoporosis risk factors and osteopenia had not been recognized and treated in our population. Adequate osteoporosis management should be implemented in patients with Crohn's disease to reduce the occurrence of osteoporotic fractures.

Coeliac disease in subjects with secondary hyperparathyroidism

ObjectiveCoeliac disease (CD) may present in its classical form with diarrhoea and weight loss, but also with atypical symptoms that are both related and unrelated to malabsorption. Osteomalacia or osteopenia following malabsorption of calcium and vitamin D is known to occur in patients with CD, and in such cases secondary hyperparathyroidism (SHP) caused by low serum calcium levels is frequently found. However, the prevalence of CD in subjects with SHP has not been reported.Material and methodsIn the Tromsø study 2001, serum parathyroid hormone (PTH) and calcium were measured in 7954 subjects of whom 6061 were eligible for follow-up. From this group, 97 subjects with SHP (serum PTH≥6.5 pmol/l and serum calcium <2.40 mmol/l) and 104 matched control subjects were re-examined with serological tests for CD (anti-tissue transglutaminase, anti-gluten IgA and IgG).ResultsCD was diagnosed in 4 subjects, all from the original SHP group. At the re-examination, only 29 of the 97 subjects with SHP still had elevated serum PTH levels. Among these were 3 of the subjects with CD. When grouping the serological test results as negative, borderline or positive, there was a significant difference between the SHP group and the controls for anti-tissue transglutaminase and anti-gluten IgA (p<0.05).ConclusionsSubjects with SHP, at least when SHP is persistent, should be tested for CD.

Progressive intrahepatic cholestasis: Mechanisms, diagnosis and therapy

Progressive intrahepatic cholestasis (PIHC, also known as progressive familial intrahepatic cholestasis) is a general term encompassing a devastating group of illnesses manifest by severe morbidity and potential mortality. By definition these diseases are characterized by persistent cholestasis that is the result of intra-hepatic rather than extra-hepatic pathology. Recent scientific advances have begun to clarify the molecular basis of many of these disorders. The morbidities of these diseases are primarily the result of profound cholestasis. This cholestasis is often associated with intractable pruritus, which leads to a very poor quality of life. Normal development and sleep are not possible for the affected individual and family dynamics are sometimes irreparably damaged. The cholestasis also leads to complications of fat soluble vitamin malabsorption including osteopenia and pathologic bone fractures, xeropthalmia, and peripheral neuropathy. End-stage liver disease and all of its attendant problems may develop in affected individuals by young adulthood. Optimal therapeutic approaches to PIHC are not well established and disease-specific approaches may be required.

Genetically heterogeneous selective intestinal malabsorption of vitamin B12: founder effects, consanguinity, and high clinical awareness explain aggregations in Scandinavia and the Middle East.

Selective intestinal malabsorption of vitamin B(12) causing juvenile megaloblastic anemia (MGA; MIM# 261100) is a recessively inherited disorder that is believed to be rare except for notable clusters of cases in Finland, Norway, and the Eastern Mediterranean region. The disease can be caused by mutations in either the cubilin (CUBN; MGA1; MIM# 602997) or the amnionless (AMN; MIM# 605799) gene. To explain the peculiar geographical distribution, we hypothesized that mutations in one of the genes would mainly be responsible for the disease in Scandinavia, and mutations in the other gene in the Mediterranean region. We studied 42 sibships and found all cases in Finland to be due to CUBN (three different mutations) and all cases in Norway to be due to AMN (two different mutations), while in Turkey, Israel, and Saudi Arabia, there were two different AMN mutations and three different CUBN mutations. Haplotype evidence excluded both CUBN and AMN conclusively in five families and tentatively in three families, suggesting the presence of at least one more gene locus that can cause MGA. We conclude that the Scandinavian cases are typical examples of enrichment by founder effects, while in the Mediterranean region high degrees of consanguinity expose rare mutations in both genes. We suggest that in both regions, physician awareness of this disease causes it to be more readily diagnosed than elsewhere; thus, it may well be more common worldwide than previously thought.

Tropical Sprue.

Tropical sprue is a disease that causes progressive villus atrophy in the small intestine, similar to nontropical (celiac) sprue. The loss of intestinal villi profoundly affects intestinal absorptive function, and patients with tropical or nontropical sprue present with malabsorption. Whereas the etiology of celiac sprue has been elucidated in considerable detail, the etiology of tropical sprue remains obscure. The favored hypothesis is that the disease is either initiated or sustained by a still-undefined infection. Patients with tropical sprue typically present with macrocytic anemia due to malabsorption of folate and/or vitamin B(12). Treatment of tropical sprue with folic acid replacement was introduced more than 50 years ago and has become standard medical treatment. Vitamin B(12) replacement is usually added if there is evidence of B(12) deficiency or malabsorption. Treatment of tropical sprue with folate and B(12) cures the macrocytic anemia and the accompanying glossitis, and often results in increased appetite and weight gain. However, even prolonged treatment with these vitamins fails to restore villus atrophy, and malabsorption usually persists. The benefit of antibiotic treatment of tropical sprue was first documented during World War II, when sulfonamides were used to treat epidemics of tropical sprue in British and Italian troops in India. Antibiotic treatment has since become the standard treatment, and tetracycline has replaced sulfonamides. The recommended length of treatment with tetracycline is 6 months and it is given in combination with folate. The treatment has been shown to normalize mucosal structure in the small intestine and resolve malabsorption in most patients with tropical sprue. However, there is a substantial relapse rate in treated patients who return to, or remain in, endemic areas in the tropics.

Tapering duodenoplasty and Roux-en-Y duodenojejunostomy in the management of adult megaduodenum

CASE REPORT A 41-year-old man with a history of chronic diarrhea and fatty stools since childhood and an inability to gain weight presented with C6 and T3 vertebral fractures. A bone mineral density scan of the lumbar spine from L2 to L4 was 61% of predicted, which was 4.3 standard deviations below the mean for an individual his age. An extensive endocrine work-up revealed a parathyroid hormone level of 4.1 and a serum calcium level of 7.8 mg/dL with an albumin of 3.5 g/dL. Based on these findings, malabsorption of vitamin D was suspected to be the cause of his bone disease. He underwent an upper gastrointestinal series that revealed a massively dilated duodenum (Fig 1). The remainder of his gastrointestinal evaluation was unremarkable. Based on these finding and our clinical suspicion that his bone disease and malabsorption were a direct result of megaduodenum and bacterial overgrowth, the patient was surgically explored. The duodenum was approxi-

Calcium balance in cystic fibrosis

Osteoporosis and osteopenia are emerging clinical problems in cystic fibrosis (CF) and, although the causes are multifactorial, they include malabsorption of vitamin D, reduced physical activity, and corticosteroid therapy. Schulze et al have studied calcium balance in girls with CF using an intravenous calcium stable isotope test and their results show that the endogenous fecal losses of calcium are increased, especially in girls with poorer nutrition, high pancreatic enzyme dosages, and those taking gastric acid inhibitors. The mechanism of these increased losses is not yet known, but the authors advance the theory that there may be increased intestinal permeability to calcium in CF due to altered function of the intestinal epithelial tight junctions.

Bile acids: from genomics to disease and therapyEdited by G. Paumgartner, D. Keppler, U. Leuschner, and A. Stiehl. 320 pp. $181.00. Kluwer Academic Publishers: the Netherlands, 2003. ISBN 0-79238-781-3. Web address for ordering: www.wkap.nl

Bile acids: from genomics to disease and therapyEdited by G. Paumgartner, D. Keppler, U. Leuschner, and A. Stiehl. 320 pp. $181.00. Kluwer Academic Publishers: the Netherlands, 2003. ISBN 0-79238-781-3. Web address for ordering: www.wkap.nl

Bone loss associated with gastrointestinal disease: prevalence and pathogenesis.

Decreased bone mineral density is a frequent finding in gastrointestinal disease. Factors contributing to this are (1) malabsorption of vitamin D, calcium and possibly vitamin K and other nutrients; (2) treatment with glucocorticoids; (3) inflammatory cytokines in inflammatory bowel disease; and (4) hypogonadism induced by gastrointestinal disease. A low bone mineral density has been reported in (1) patients who have undergone gastrectomy (27-44% with Z-scores of < -1); (2) pernicious anaemia; (3) coeliac disease (8-22% with Z-scores of < -2); (4) Crohn's disease (mean 32-38% with Z-scores of < -1); and (5) ulcerative colitis (mean 23-25% with Z-scores of < -1). Reduced bone mineral density is thus prevalent in these individuals and is compounded by age related bone loss, leading to the development of severe bone disease in some patients.

Innate immunity and coeliac disease

Coeliac disease is an inflammatory disorder of the small intestine that is triggered by dietary gluten (the storage proteins of wheat) and related cereals like rye and barley. T-cell infiltration in the intestinal epithelium and the underlying stroma can lead to complete destruction of the microscopic villi of the small intestine, with consequent malabsorption of nutrients, vitamins, and minerals. Whilst the classic presentation of coeliac disease with diarrhoea and malabsorption has become relatively rare (prevalence from 1 in 2000 to 1 in 10000 in the west), atypical, oligosymptomatic, or even asymptomatic manifestations (with patients having villous flattening of various degrees) are frequent, with an estimated prevalence of 1 in 200 in Europe and the USA, making coeliac disease one of the most common inherited disorders.

Molecular genetics of 3beta-hydroxy-Delta5-C27-steroid oxidoreductase deficiency in 16 patients with loss of bile acid synthesis and liver disease.

The 3beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase (C(27) 3beta-HSD) is a membrane-bound enzyme of the endoplasmic reticulum that catalyzes an early step in the synthesis of bile acids from cholesterol. Subjects with autosomal recessive mutations in the encoding gene, HSD3B7, on chromosome 16p11.2-12 fail to synthesize bile acids and develop a form of progressive liver disease characterized by cholestatic jaundice and malabsorption of lipids and lipid-soluble vitamins from the gastrointestinal tract. The gene encoding the human C(27) 3beta-HSD enzyme was isolated previously, and a 2-bp deletion in exon 6 of HSD3B7 was identified in a well characterized subject with this disorder. Here, we report a molecular analysis of 15 additional patients from 13 kindreds with C(27) 3beta-HSD deficiency. Twelve different mutations were identified in the HSD3B7 gene on chromosome 16p11.2-12. Ten mutations were studied in detail and shown to cause complete loss of enzyme activity and, in two cases, alterations in the size or amount of the transcribed mRNA. Mutations were inherited in homozygous form in 13 subjects from 10 families and compound heterozygous form in four subjects from three families. We conclude that a diverse spectrum of mutations in the HSD3B7 gene underlies this rare form of neonatal cholestasis.