Vitamin E deficiency and neurologic disease in adults with cystic fibrosis

We report the cases of two adult patients with cystic fibrosis affecting the pancreas and liver, who also had severe vitamin E deficiency and neurologic disease. The most prominent clinical features were abnormal eye movements, diminished reflexes, decreased vibratory and position sense, ataxia, and muscle weakness. Treatment with intramuscular injections of vitamin E partially corrected the neurologic deficits. Vitamin E absorption tests documented severe malabsorption, which was later alleviated by the addition of dessicated ox bile to the regimen of alpha-tocopheryl acetate. These studies suggest that a decreased intraluminal concentration of bile salts is an important factor in the development of severe vitamin E deficiency and in the poor response to oral replacement therapy that is seen in some patients with cystic fibrosis.     

Vitamin E deficiency and impaired cellular immunity related to intestinal fat malabsorption.

This report describes a patient in whom a severe vitamin E deficiency developed secondary to an intestinal malabsorptive disorder. In vivo and in vitro impairment of T-cell function, as well as a polyneuropathy, were observed in conjunction with this vitamin deficiency. Repletion of the vitamin deficiency was associated with marked improvement in the T-cell functions and modest improvement in the neuropathy. Observations in this patient suggest that severe vitamin E deficiency in humans may impair T-cell activity and that correction of the deficient state may reverse these T-cell abnormalities. Further studies will need to be performed to confirm these findings.     

Vitamin E deficiency and its clinical significance in adults with primary biliary cirrhosis and other forms of chronic liver disease

The vitamin E status of 146 adults with chronic liver disease was assessed by estimating both their serum vitamin E concentration and the ratio of serum vitamin E to serum cholesterol concentration. Low levels of vitamin E occurred most frequently in patients with primary biliary cirrhosis and other forms of chronic cholestatic liver disease. When a serum vitamin E concentration of 12.3 mumol/l (mean-2 SD of a control population) was taken as the lower limit of normal, 44% of patients with primary biliary cirrhosis and 32% with other chronic cholestatic liver disease had a reduced concentration, indicating a biochemical deficiency of vitamin E. If a vitamin E/total cholesterol ratio of 2.35 mumol/mmol was taken as the lower limit of normal, then 64% and 43% of patients with primary biliary cirrhosis and other chronic cholestatic liver disease, respectively, had a biochemical deficiency of vitamin E. Of the patients with chronic cholestasis and a serum bilirubin concentration greater than 100 mumol/l, 91% had a reduced vitamin E/cholesterol ratio. Twelve patients with primary biliary cirrhosis and severe vitamin E deficiency (serum vitamin E less than 5.0 mumol/l and a vitamin E/cholesterol ratio less than 1.0 mumol/mmol) underwent extensive neurological investigation. Five had a mild mixed sensorimotor peripheral neuropathy, which was not, however, typical of the neurological syndrome associated with vitamin E deficiency. In patients with severe biochemical deficiency of vitamin E (less than 5 mumol/l and less than 1 mumol/mmol total cholesterol), administration of large oral doses of vitamin E only increased serum concentrations to within the normal range in one patient; in the others even weekly parenteral administration over a 3-month period did not correct deficiency. In patients with less severe biochemical deficiency, the serum vitamin E concentration and vitamin E/total cholesterol ratio were restored to normal by oral or intramuscular supplements of the vitamin.     

Vitamin E deficiency in primary biliary cirrhosis: gastrointestinal malabsorption, frequency and relationship to other lipid-soluble vitamins

In contrast to deficiencies of vitamins A, D and K, little is known of the prevalence, clinical manifestations and mechanisms of vitamin E deficiency in adult patients with cholestasis. We measured serum vitamin E levels in 45 patients with primary biliary cirrhosis, 20 with primary sclerosing cholangitis, 9 with cryptogenic cirrhosis and 12 with alcoholic cirrhosis. To correct for the hyperlipidemia often found in patients with primary biliary cirrhosis and primary sclerosing cholangitis, total serum lipids were measured and vitamin E levels were expressed as the vitamin E/total serum lipid ratio. Serum vitamin A and D levels and prothrombin time were also determined. Six of 45 patients with primary biliary cirrhosis (13%) but none of the patients with sclerosing cholangitis, cryptogenic cirrhosis or alcoholic cirrhosis and subnormal vitamin E/total serum lipids ratios. Vitamin E deficiency was found in two of eight patients with asymptomatic primary biliary cirrhosis. There was no correlation between standard liver biochemical tests, fasting serum cholylglycine and vitamin E levels. Patients with primary biliary cirrhosis and primary sclerosing cholangitis had significantly lower vitamin E/total serum lipids ratios than patients with either cryptogenic or alcoholic cirrhosis. Twenty-three percent of patients with primary biliary cirrhosis were vitamin D deficient and 14% had low vitamin A levels. Two of the six patients with vitamin E deficiency were also deficient in vitamin D, only one was vitamin A deficient and none had prolonged prothrombin time. We also investigated the gastrointestinal absorption of vitamin E in nine patients with primary biliary cirrhosis and normal vitamin E levels as well as in six normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Familial isolated vitamin E deficiency. Extensive study of a large family with a 5-year therapeutic follow-up

Summary A major neurological deterioration, beginning with ataxia, led to the diagnosis of familial vitamin E deficiency in a girl. Based upon vitamin E determinations, 4/8 members of the (consanguineous) sibship were considered to be homozygous. Homozygosity was also found for the alleles of six markers linked to theAVED locus, recently identified in similar Tunisian or Sicilian families on chromosome 8q. Measures of vitamin E in lipoprotein fractions and in liver biopsy after vitamin E oral load suggested that free diffusion of vitamin E between the different compartments was possible and even increased. However, a high-affinity ligand seemed to be lacking, either in the hepatic recycling of vitamin E or in both the hepatic and the other vitamin E compartments. The 5-year substitutive treatment was successful only in the pre- or paucisymptomatic patients. Serum vitamin E must be measured in any unexplained progressive ataxia.     

Encéphalopathie de Gayet Wernicke associée à une encéphalopathie pellagrique : complication rare et inhabituelle chez une femme âgée hospitalisée pour pneumopathie d’inhalation

Introduction

Wernicke's encephalopathy caused by thiamine deficiency is typically characterised by a mental-status change, oculomotor dysfunction and an ataxia. Pellagra is the clinical presentation of niacin deficiency comprising cutaneous, gastrointestinal and neuropsychiatric manifestations.

Observation

We report a case of encephalopathy due to dual vitamin deficiency of both thiamine (vitamin B1) and niacin (vitamin PP) in an 80-year-old women, hospitalized for severe sepsis caused by aspiration pneumonia. Severe malnutrition and alcohol consumption pointed to a diagnosis of vitamin deficiency. The clinical presentation and magnetic resonance imaging (MRI) were compatible with Wernicke's encephalopathy that remained irreversible despite vitamin B1 supplementation. Niacin supplementation allowed for complete regression of the observed symptoms compatible with niacin deficiency.

Conclusion

Malnourished and alcoholic patients showing signs of encephalopathy should receive supplemental multivitamins including niacin.     

Protective links between vitamin D,inflammatory bowel disease and colon cancer

Vitamin D deficiency has been associated with a wide range of diseases and multiple forms of cancer including breast, colon, and prostate cancers. Relatively recent work has demonstrated vitamin D to be critical in immune function and therefore important in inflammatory diseases such as inflammatory bowel disease(IBD). Because vitamin D deficiency or insufficiency is increasingly prevalent around the world, with an estimated 30%-50% of children and adults at risk for vitamin D deficiency worldwide, it could have a significant impact on IBD. Epidemiologic studies suggest that low serum vitamin D levels are a risk factor for IBD and colon cancer, and vitamin D supplementation is associated with decreased colitis disease activity and/or alleviated symptoms. Patients diagnosed with IBD have a higher incidence of colorectal cancer than the general population, which supports the notion that inflammation plays a key role in cancer development and underscores the importance of understanding how vitamin D influences inflammation and its cancer-promoting effects. In addition to human epidemiological data, studies utilizing mouse models of colitis have shown that vitamin D is beneficial in preventing or ameliorating inflammation and clinical disease. The precise role of vitamin D on colitis is unknown; however, vitamin D regulates immune cell trafficking and differentiation, gut barrier function and antimicrobial peptide synthesis, all of which may be protective from IBD and colon cancer. Here we focus on effects of vitamin D on inflammation and inflammation-associated colon cancer and discuss the potential use of vitamin D for protection and treatment of IBD and colon cancer.     

Hyperparathyroidism and complications associated with vitamin D deficiency in HIV-infected adults in New York City, New York

Although recent studies report a high prevalence of vitamin D deficiency in HIV-infected adults similar to that in the general population, metabolic complications of vitamin D deficiency may be worsened with HIV infection and remain insufficiently characterized. We conducted a retrospective cross-sectional cohort study to determine prevalence and correlates of vitamin D deficiency and hyperparathyroidism among HIV-infected patients attending an urban clinic. Vitamin D deficiency was defined as 25(OH)-vitamin D <20 ng/ml and insufficiency as 20 to <30 ng/ml, and hyperparathyroidism as parathyroid-hormone >65 pg/ml. We used the X(2) test to compare proportions and logistic regression to assess for associations. Among 463 HIV-infected patients, the prevalence of vitamin D deficiency was 59%. The prevalence of hyperparathyroidism was 30% among patients with vitamin D deficiency, 23% among those with insufficiency, and 12% among those with sufficient vitamin D levels. Vitamin D deficiency was associated with increased odds of hyperparathyroidism. Severe vitamin D deficiency was associated with elevated alkaline phosphatase, a marker for increased bone turnover. Although efavirenz use was associated with vitamin D deficiency, and protease inhibitor use with decreased odds of vitamin D deficiency, there was no statistical difference in rates of hyperparathyroidism stratified by combination antiretroviral therapy (cART) use. Given the increased risk of osteopenia with HIV infection and cART use, vitamin D supplementation for all HIV-infected patients on cART should be prescribed in accordance with the 2011 Endocrine Society guidelines. In HIV-infected patients with severe vitamin D deficiency or hyperparathyroidism, screening for osteomalacia and osteopenia may be warranted.     

Hemoglobin E diseases: Hematological,analytical, and biosynthetic studies in homozygotes and double heterozygotes for α-thalassemia

Two families with Hb E diseases are described. In the Laotian family S, three homozygous Hb E were found. In the Vietnamese family H, double heterozygous Hb E-α-thalassemia-2 and Hb E-Hb H diseases were found. Anemia or hemolysis was absent in Hb E carriers, unless complicated by iron deficiency, the presence of severe α-thalassemia gene (Hb H disease), or oxidative drug (paraaminosalicylic acid). Moreover, iron deficiency or concurrent α-thalassemia genes resulted in a decreased amount of Hb E in its heterozygous carriers. Mild microcytosis and hypochromia were observed in Hb E heterozygotes, whereas the microcytosis and hypochromia were more pronounced in Hb E homozygotes. Globin chain synthesis studies yielded unbalanced α/non-α ratios in both heterozygotes and homozygotes (average ratios were 1.13 and 1.56, respectively). The unbalanced biosynthetic ratios with microcytosis and hypochromia in Hb E carriers represented a β-thalassemia phenotype, which could be a result of reduced synthesis of β^E-globin mRNA, as suggested by recent hybridization studies.     

Crystal structure of human alpha-tocopherol transfer protein bound to its ligand: implications for ataxia with vitamin E deficiency

Human alpha-tocopherol (alpha-T) transfer protein (ATTP) plays a central role in vitamin E homeostasis, preventing degradation of alpha-T by routing this lipophilic molecule for secretion by hepatocytes. Mutations in the gene encoding ATTP have been shown to cause a severe deficiency in alpha-T, which results in a progressive neurodegenerative spinocerebellar ataxia, known as ataxia with vitamin E deficiency (AVED). We have determined the high-resolution crystal structure of human ATTP with (2R,4'R,8'R)-alpha-T in the binding pocket. Surprisingly, the ligand is sequestered deep in the hydrophobic core of the protein, implicating a large structural rearrangement for the entry and release of alpha-T. A comparison to the structure of a related protein, Sec14p, crystallized without a bona fide ligand, shows a possibly relevant open conformation for this family of proteins. Furthermore, of the known mutations that cause AVED, one mutation, L183P, is located directly in the binding pocket. Finally, three mutations associated with AVED involve arginine residues that are grouped together on the surface of ATTP. We propose that this positively charged surface may serve to orient an interacting protein, which might function to regulate the release of alpha-T through an induced change in conformation of ATTP.     

Fat-soluble vitamin levels in patients with primary biliary cirrhosis

OBJECTIVE: To determine the occurrence of fat-soluble vitamin deficiencies and to identify clinical factors that may predict vitamin deficiency in patients with primary biliary cirrhosis (PBC). METHODS: Review of our data from a randomized, placebo-controlled trial that evaluated the efficacy of UDCA in 180 patients with PBC. We use the first available measurements of vitamin levels in each study participant. Vitamin levels for A, D, and E were measured in serum. The prothrombin time (PT) was used as a surrogate marker for vitamin K. RESULTS: The proportion of patients with fat-soluble vitamin deficiencies in the treatment and placebo groups was similar and the data sets were combined. The proportion with vitamin A, D, E or K deficiency was 33.5%, 13.2%, 1.9%, and 7.8%, respectively. In multivariate analysis, the Mayo risk score, advanced histological stage, and total cholesterol were independently associated with vitamin A deficiency whereas serum albumin levels was independently associated with vitamin D deficiency. No factors were associated with vitamin E or K deficiency in multivariate analysis owing to the few vitamin E and K deficient patients. Factors predictive of vitamin K deficiency by univariate analysis included Mayo risk score, advanced histological stage, HDL, total bilirubin, AST, and albumin. The cut-off value of the Mayo risk score with the highest sensitivity and specificity for vitamin A deficiency was 5.0. CONCLUSION: Other than deficiency of vitamin A, deficiency of fat-soluble vitamins occurs uncommonly in patients with PBC. A Mayo risk score > or = 5 helps in selecting patients with PBC for surveillance for vitamin A deficiency.     

Management of nutritional problems in subacute care

Poor nutritional status is one of the major factors associated with functional decline and mortality in older persons. Older persons are at increased risk for malnutrition because of the physiologic anorexia of aging. During a stay in a subacute care facility, attention to nutrition is a major component of the rehabilitative process. The pathophysiology of malnutrition, diagnostic techniques available to diagnose malnutrition, causes and management of protein energy malnutrition, specific nutritional problems caused by vitamin and trace element deficiency, and nutritional management of specific diseases (e.g., hip fracture and diabetes mellitus) are reviewed.     

Review: vitamin D, immunity and lupus

The identification of vitamin D receptor in cells involved in the immune response and the discovery that activated dendritic cells produce vitamin D hormone suggested that vitamin D could exert immunoregulatory effects. Patients with autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus (SLE) show low 25-OH vitamin D serum levels. In particular, SLE patients have multiple risk factors for vitamin D deficiency and disease severity seems correlated with lower 25-OH vitamin D serum levels. Treatment of vitamin D deficiency could be particularly important in SLE patients due to concomitant insults on their tissues such as bone, and in view of the possible immunomodulatory effects exerted by vitamin D.     

The role of cholesterol and intermediary metabolites of its synthesis in intensive care and parenteral nutrition

Hypocholesterolaemia is a frequent and typical phenomenon of many acute situations such as injury, severe infection associated with sepsis and septic shock, catabolic situations after serious operations, in myocardial infarction and neoplastic diseases. This phenomenon cannot be explained only by malnutrition or energy deficiency although they may participate in the development of hypocholesterolaemia. In the development of the mentioned acute conditions participates according to our opinion also impaired synthesis of cholesterol as well as of intermediary metabolites of its biosynthesis (isoprene, squalene, lanosterol, and lathosterol). Evidence was provided that deprivation of these metabolites is frequent, very marked and statistically significant. Some precursors of cholesterol biosynthesis are extremely important for normal processes in the cell and as mediators (isoprene, farnesyl diphosphate, squalene). Their deficiency is a serious disorder which must be diagnosed in time. It is important to define the patients and conditions where a serious deficiency of these metabolites develops regularly and to seek ways how to treat deprivation of the mentioned metabolites.     

Increased atherosclerosis in hyperlipidemic mice deficient in alpha -tocopherol transfer protein and vitamin E

Although lipid peroxidation in the subendothelial space has been hypothesized to play a central role in atherogenesis, the role of vitamin E in preventing lipid peroxidation and lesion development remains uncertain. Here we show that in atherosclerosis-susceptible apolipoprotein E knockout mice, vitamin E deficiency caused by disruption of the alpha-tocopherol transfer protein gene (Ttpa) increased the severity of atherosclerotic lesions in the proximal aorta. The increase was associated with increased levels of isoprostanes, a marker of lipid peroxidation, in aortic tissue. These results show that vitamin E deficiency promotes atherosclerosis in a susceptible setting and support the hypothesis that lipid peroxidation contributes to lesion development. Ttpa(-/-) mice are a genetic model of vitamin E deficiency and should be valuable for studying other diseases in which oxidative stress is thought to play a role.     

Acquired isolated factor VII deficiency associated with severe bleeding and successful treatment with recombinant FVIIa (NovoSeven).

Acquired isolated FVII deficiency not due to vitamin K deficiency or liver disease is rare and often associated with severe bleeding. We present a case of transient acquired factor VII deficiency associated with major bleeding, successfully treated with twice daily intermittent intravenous recombinant activated factor VII (rFVIIa) (NovoSeven; Novo Nordisk). The severe transient reduction in factor VII coagulant activity (FVII:C) levels, unresponsive to fresh frozen plasma and vitamin K administration, raise the possibility of an acquired inhibitor to factor VII. However, no inhibitor to factor VII could be demonstrated using protein G sepharose adsorption, or a Bethesda assay using IgG purified from patient plasma. There are few reports of the use of rFVIIa in this setting and this case suggests that rFVIIa is effective therapy, and should be considered early when acquired factor VII deficiency is associated with severe bleeding.     

Primary hyperparathyroidism and vitamin D deficiency

Primary hyperparathyroidism (PHPT) and vitamin D (VD) deficiency are frequent conditions due to the widespread application of assays for calcium and VD. PHPT presentation is dominated by diversity in its expression and the current predominance of asymptomatic forms. VD, which plays a major role in calcium and phosphate homeostasis, is also involved in many physiological processes in this disease, such as lipid and glucose metabolism, and in the signalling pathways and functioning of many cell types. The bone and cardiometabolic complications described in PHPT are exacerbated by vitamin D deficiency, the prevalence of which varies according to many parameters (environment, skin pigmentation, associated chronic diseases, liver and kidney function, assay kit used, etc.). In response to this observation, experts in field from medical societies validated the indication for systematic assay of VD occurring with PHPT and the need for replacement in case of deficiency. Several epidemiological studies have confirmed that replacement with natural vitamin D is well tolerated and safe in subjects with PHPT and VD deficiency. This supplementation reduces hyperparathormonemia, does not have symptomatic effects on calciuria, and especially improves the bone and functional condition of patients.     

Vitamin D Status and Supplementation in the Critically Ill

Vitamin D deficiency has recently been recognized as a widespread global disorder. Generally considered a direct extension of malnutrition, even subclinical hypovitaminosis D is now recognized in adequately nourished populations. Compared to the general population, the prevalence of hypovitaminosis D is greater in the critically ill population. In fact, several studies have shown poorer outcomes in critically ill patients discovered to be vitamin D deficient or insufficient. Controversy persists regarding vitamin D measurements, quantity of supplementation, and appropriate target level in various populations. Vitamin D has a vital role in calcium homeostasis and extra-skeletal health, such as immune function. Therefore, vitamin D supplementation may have a role for improving outcomes in critically ill patients. In this review, we will first discuss the metabolism and function of vitamin D under normal physiologic conditions. We will then explore the prevalence and prognostic value of vitamin D deficiency in critical illness. Finally, we will examine recent trials focusing on appropriate dosing, route of administration, and outcomes associated with vitamin D supplementation in the ICU.     

Nutrition and liver diseases

Malnutrition and micronutrient deficiencies are common in patients with liver diseases. The pathogenesis of protein-energy malnutrition in cirrhosis involves many factors, including poor oral intake, malabsorption, and metabolic abnormalities similar to stress. Encephalopathy may complicate cirrhosis but is usually not caused by diet. Protein restriction is only necessary in rare patients with refractory encephalopathy. The use of branched-chain amino-acid solutions is not supported by the literature. Chronic liver diseases without cirrhosis are not usually associated with protein-energy malnutrition, but vitamin and mineral deficiencies are common, especially with significant cholestasis. Fatty liver may result from excessive triglyceride uptake and production by the liver or by a secretory defect. Therapy for fatty liver depends on its cause. Chronic total parenteral nutrition may induce fatty liver and inflammation especially in patients with short-bowel syndrome. Deficiency of choline in parenteral nutrition has been proposed as the mechanism for liver disease. Acute liver diseases such as fulminant hepatic failure or alcoholic hepatitis are considered hypercatabolic diseases and thus require prompt nutritional intervention with a high-calorie enteral or parenteral formula. In fulminant hepatic failure, low-protein, fluid-restricted formulas are recommended.