Chronic pancreatitis and nutritional support.

Malnutrition in patients with chronic pancreatitis is common, but its evaluation is often missed in clinical practice. Pancreatic exocrine insufficiency is the single most important cause of malnutrition; therefore, it needs to be screened for and treated appropriately. Specific diet regimens in patients suffering from chronic pancreatitis are rarely reported in the literature. Patients suffering from chronic pancreatitis have a higher demand for energy but a lower caloric intake secondary to pancreatic exocrine insufficiency, combined with the malabsorption of liposoluble vitamin and micronutrients, which needs be corrected by appropriate dietary counselling. Diabetes is frequently observed in chronic pancreatitis and classified as type 3c, which is characterized by low levels of both serum insulin and glucagon; therefore, there is a tendency towards hypoglycaemia in patients treated with insulin. Diabetes contributes to malnutrition in chronic pancreatitis. Strategies to treat exocrine and endocrine insufficiency are important to achieve better control of the disease.

Pancreatic insufficiency as a complication of type 1 diabetes causing enteric hyperoxaluria in a transplant kidney.

A kidney transplant recipient with a medical history of type 1 diabetes mellitus (T1DM) presents to the clinic with an acute kidney injury (AKI) and diarrhoea. Kidney biopsy found deposition of focal oxalate crystals, and further investigation revealed a raised 24-hour urinary oxalate and reduced faecal elastase. Therefore, we present a case of acute oxalate nephropathy (AON) secondary to enteric hyperoxaluria as a result of pancreatic insufficiency caused by T1DM. T1DM is a common cause of end-stage renal failure and exocrine pancreatic insufficiency. Therefore, AON secondary to enteric hyperoxaluria should be considered in patients with a transplant AKI. Earlier testing of 24-hour urinary oxalate and faecal elastase could generate diagnosis before biopsy results and allow commencement of pancreatic replacement therapy earlier to avoid permanent loss of kidney function.

The impact of nutritional status on pancreatic cancer therapy.

INTRODUCTION: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive disease with poor outcomes. One of the reasons for the dismal prognosis resides in its impressive ability to alter the nutritional status of patients who develop malnutrition, cachexia, anorexia, and sarcopenia in most cases. The ideal way to measure such changes in PDAC patients, in order to readily identify them and avoid complications or discontinuations of treatment is a relatively unexplored area. In addition, most PDAC patients experience pancreatic exocrine insufficiency (PEI) that contributes to the complex puzzle of malnutrition and that can be treated with Pancreatic Enzyme Replacement Therapy (PERT). AREAS COVERED: We review current knowledge on the impact of nutritional status on both surgical and medical treatments for PDAC, reporting available data on the causes of malnutrition, characteristics, and advantages of different tools to investigate nutritional status and possible strategies to improve patient outcomes. EXPERT OPINION: All PDAC patients should receive a careful nutritional assessment at diagnosis, and this should be repeated alongside their treatment path. Screening tools and biochemical variables or scores are associated with prognosis, but bioimpedance vector analysis (BIVA) and radiological assessment of body composition seem more accurate in predicting clinical outcomes and postoperative complications.

Fat-Soluble Vitamin Deficiencies and Disruption of the Immune System in Pancreatic Cancer: A Vicious Cycle.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is currently an increasing contributor to cancer-related mortality. Despite advances in cancer treatment, PDAC survival rates have remained roughly unchanged over the years. Specifically, late diagnosis and insensitivity to currently available therapeutic regimens have been identified as the main causes for its poor survival. Pancreatic exocrine insufficiency (PEI) is a typical complication associated with PDAC diagnosis and pancreatic surgery. Pancreatic exocrine insufficiency, a major contributor to maldigestion in PDAC, is often not treated because it remains undetected because of lack of overt signs and symptoms. In this review, we will focus on the major consequences of PEI, including the inadequacy of lipase excretion, which results in deficiency of fat-soluble vitamins. Because PDAC is known for its immune-high jacking mechanisms, we describe key features in which deficiencies of fat-soluble vitamins may contribute to the aggressive biological behavior and immune evasion in PDAC. Because PEI has been shown to worsen survival rates in patients with PDAC, detecting PEI and the related fat-soluble vitamin deficits at the time of PDAC diagnosis is critical. Moreover, timely supplementation of pancreatic enzymes and fat-soluble vitamins may improve outcomes for PDAC patients.

Vitamin E supplementation in people with cystic fibrosis.

BACKGROUND: People with cystic fibrosis are at an increased risk of fat-soluble vitamin deficiency, including vitamin E. Vitamin E deficiency can cause a host of conditions such as haemolytic anaemia, cerebellar ataxia and cognitive difficulties. Vitamin E supplementation is widely recommended for people with cystic fibrosis and aims to ameliorate this deficiency. This is an updated version of the review. OBJECTIVES: To determine the effects of any level of vitamin E supplementation on the frequency of vitamin E deficiency disorders in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Group's Cystic Fibrosis Trials Register and also searched international online trial registries for any ongoing clinical trials that were not identified during our register search. Date of last search of the Register: 11 August 2020. Date of last search of international online trial registries: 20 July 2020. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing any preparation of vitamin E supplementation to placebo or no supplement, regardless of dosage or duration. DATA COLLECTION AND ANALYSIS: Two authors extracted outcome data from each study (published information) and assessed the risk of bias of each included study. They assessed the quality of the evidence using GRADE. MAIN RESULTS: Four studies with a total of 141 participants were included in the review, two of these were in children (aged six months to 14.5 years), and two did not specify participants' age. All studies used different formulations and doses of vitamin E for various durations of treatment (10 days to six months). Two studies compared the supplementation of fat-soluble as well as water-soluble formulations to no supplementation in different arms of the same study. A third study compared a water-soluble formulation to a placebo; and in the fourth study a fat-soluble formulation of vitamin E was assessed against placebo. There was limited detail about randomisation and blinding in the included studies which compromises the quality of the evidence base for the review. The heterogeneous mix of the formulations with differing biovailabilities among these studies also limits the generalisability of the data to the wider cystic fibrosis population. None of the studies in either comparison report the review's primary outcomes of vitamin E total lipid ratio or the incidence of vitamin E-specific deficiency disorders, or the secondary outcomes lung function or quality of life. Water-soluble vitamin E Water-soluble vitamin E may improve serum vitamin E levels compared with control at six months, one study (45 participants), mean difference (MD) 19.74 umol/L (95% confidence interval (CI) 13.48 to 26.00) (low-quality evidence). Similar results were also seen at one month, two studies (32 participants), MD 17.66 umol/L (95% CI 10.59 to 24.74) and at three months, one study (45 participants), MD 11.61 umol/L (95% CI 4.77 to 18.45). Only one study (45 participants) reported weight (secondary outcome of growth and nutritional status) at one and six months, but showed no difference between treatment and control at either time point. Fat-soluble vitamin E Two studies (36 participants) reported higher levels of serum vitamin E at one month with fat-soluble vitamin E compared with control, MD 13.59 umol/L (95% CI 9.52 to 17.66); however, at three months one study (36 participants) showed no difference between treatment and control. No studies in this comparison reported on growth or nutritional status. AUTHORS' CONCLUSIONS: Vitamin E supplementation may lead to an improvement in vitamin E levels in people with cystic fibrosis, although evidence we assessed was low quality. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy. In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal clinical effectiveness.

Improved residual fat malabsorption and growth in children with cystic fibrosis treated with a novel oral structured lipid supplement: A randomized controlled trial.

BACKGROUND: In the primary analysis of a 12-month double-blind randomized active placebo-controlled trial, treatment of children with cystic fibrosis (CF) and pancreatic insufficiency (PI) with a readily absorbable structured lipid (Encala™, Envara Health, Wayne, PA) was safe, well-tolerated and improved dietary fat absorption (stool coefficient of fat absorption [CFA]), growth, and plasma fatty acids (FA). OBJECTIVE: To determine if the Encala™ treatment effect varied by severity of baseline fat malabsorption. METHODS: Subjects (n = 66, 10.5±3.0 yrs, 39% female) with baseline CFA who completed a three-month treatment with Encala™ or a calorie and macronutrient-matched placebo were included in this subgroup analysis. Subjects were categorized by median baseline CFA: low CFA (<88%) and high CFA (≥88%). At baseline and 3-month evaluations, CFA (72-hour stool, weighed food record) and height (HAZ), weight (WAZ) and BMI (BMIZ) Z-scores were calculated. Fasting plasma fatty acid (FA) concentrations were also measured. RESULTS: Subjects in the low CFA subgroup had significantly improved CFA (+7.5±7.2%, mean 86.3±6.7, p = 0.002), and reduced stool fat loss (-5.7±7.2 g/24 hours) following three months of EncalaTM treatment. These subjects also had increased plasma linoleic acid (+20%), α-linolenic acid (+56%), and total FA (+20%) (p≤0.005 for all) concentrations and improvements in HAZ (0.06±0.08), WAZ (0.17±0.16), and BMIZ (0.20±0.25) (p≤0.002 for all). CFA and FA were unchanged with placebo in the low CFA group, with some WAZ increases (0.14±0.24, p = 0.02). High CFA subjects (both placebo and Encala™ groups) had improvements in WAZ and some FA. CONCLUSIONS: Subjects with CF, PI and more severe fat malabsorption experienced greater improvements in CFA, FA and growth after three months of Encala™ treatment. Encala™ was safe, well-tolerated and efficacious in patients with CF and PI with residual fat malabsorption and improved dietary energy absorption, weight gain and FA status in this at-risk group.

Influence of pancreatic status on circulating plasma sterols in patients with cystic fibrosis.

Background Patients with cystic fibrosis (CF) have a reduced intestinal absorption of cholesterol and in a preliminary study we observed differences in plasma sterol profile between patients with pancreatic sufficiency (PS) and those with pancreatic insufficiency (PI). Therefore, we hypothesized that the sterol analysis may contribute to study the digestion and absorption state of lipids in patients with CF. To this aim we evaluated plasma sterols in a significant number of adult patients with CF in relation to the pancreatic status. Methods Beside cholesterol, we measured phytosterols and lathosterol as markers of intestinal absorption and hepatic biosynthesis, respectively, by gas-chromatography in plasma of adult CF patients with pancreatic sufficiency (PS-CF, n = 57), insufficiency (PI-CF, n = 97) and healthy subjects (control group, CT, n = 71). Results PI-CF patients had cholesterol and phytosterols levels significantly lower than PS-CF and CT (p < 5 × 10-10) suggesting a reduced intestinal absorption of sterols related to PI. Instead, lathosterol was significantly higher in PI-CF patients than PS-CF and CT (p < 0.0003) indicating an enhanced cholesterol biosynthesis. In PI-CF patients, phytosterols positively correlate with vitamin E (p = 0.004). Both the classes of molecules need cholesterol esterase for the intestinal digestion, thus the reduced levels of such lipids in serum from PI-CF patients may depend on a reduced enzyme activity, despite the pancreatic enzyme supplementation in all PI-CF patients. Conclusions A plasma sterols profile may be useful to evaluate the metabolic status of lipids in adult patients with CF and could help to manage the pancreatic enzyme supplementation therapy.

Acute oxalate nephropathy due to high vitamin C doses and exocrine pancreatic insufficiency.

Oxalate kidney injury can manifest as oxalate nephropathy or nephrolithiasis and present as acute kidney injury or even as end-stage renal disease. There are several known causes for acute oxalate nephropathy; however, the combination of exocrine pancreatic insufficiency with overconsumption of vitamin C has not been described before. In this case, a man in his early 80s presented with anorexia and extreme fatigue for 1 week. He had a history of myalgic encephalomyelitis, also known as chronic fatigue syndrome, for which he took several supplements, including high doses of vitamin C. Furthermore, several years ago, he was diagnosed elsewhere with exocrine pancreatic insufficiency. On admission, acute kidney injury was diagnosed. The kidney biopsy showed oxalate nephropathy as the cause. We diagnosed acute oxalate nephropathy due to high vitamin C doses and exocrine pancreatic insufficiency. Within 14 days, his kidney function got worse and he required renal replacement therapy.

Management of Exocrine Pancreatic Insufficiency in Children.

The diagnosis of exocrine pancreatic insufficiency (EPI) can be difficult, as symptoms may be nonspecific. A delayed diagnosis of EPI can negatively impact health through poor weight gain, impaired growth, and malabsorption of nutrients. Because of active growth and development, children are more vulnerable to the consequences of untreated EPI. Pancreatic enzyme replacement therapy is the cornerstone of management and offers both symptomatic relief and improvement in clinical outcomes. Additionally, a high-energy diet with unrestricted fat and supplementation with fat-soluble vitamins is often required to optimize growth and prevent nutrition deficiencies. Cystic fibrosis (CF) is the most common condition in children that causes EPI, and improvement in nutrition management is associated with improved pulmonary function and increased survival. Currently, the management of other conditions leading to EPI in children is not well studied, and inferences from the CF literature are often necessary in caring for these patients.

Choline Supplementation in Cystic Fibrosis-The Metabolic and Clinical Impact.

BACKGROUND: Choline is essential for the synthesis of liver phosphatidylcholine (PC), parenchymal maintenance, bile formation, and lipoprotein assembly to secrete triglycerides. In choline deficiency, the liver accretes choline/PC at the expense of lung tissue, thereby impairing pulmonary PC homoeostasis. In cystic fibrosis (CF), exocrine pancreas insufficiency results in impaired cleavage of bile PC and subsequent fecal choline loss. In these patients, the plasma choline concentration is low and correlates with lung function. We therefore investigated the effect of choline supplementation on plasma choline/PC concentration and metabolism, lung function, and liver fat. METHODS: 10 adult male CF patients were recruited (11/2014⁻1/2016), and orally supplemented with 3 × 1 g choline chloride for 84 (84⁻91) days. Pre-/post-supplementation, patients were spiked with 3.6 mg/kg [methyl-D9]choline chloride to assess choline/PC metabolism. Mass spectrometry, spirometry, and hepatic nuclear resonance spectrometry served for analysis. RESULTS: Supplementation increased plasma choline from 4.8 (4.1⁻6.2) µmol/L to 10.5 (8.5⁻15.5) µmol/L at d84 (p < 0.01). Whereas plasma PC concentration remained unchanged, D9-labeled PC was decreased (12.2 [10.5⁻18.3] µmol/L vs. 17.7 [15.5⁻22.4] µmol/L, p < 0.01), indicating D9-tracer dilution due to higher choline pools. Supplementation increased Forced Expiratory Volume in 1 second percent of predicted (ppFEV1) from 70.0 (50.9⁻74.8)% to 78.3 (60.1⁻83.9)% (p < 0.05), and decreased liver fat from 1.58 (0.37⁻8.82)% to 0.84 (0.56⁻1.17)% (p < 0.01). Plasma choline returned to baseline concentration within 60 h. CONCLUSIONS: Choline supplementation normalized plasma choline concentration and increased choline-containing PC precursor pools in adult CF patients. Improved lung function and decreased liver fat suggest that in CF correcting choline deficiency is clinically important. Choline supplementation of CF patients should be further investigated in randomized, placebo-controlled trials.

Nutritional Status in the First 2 Years of Life in Cystic Fibrosis Diagnosed by Newborn Screening.

OBJECTIVE: To evaluate nutritional status and associated factors in a cystic fibrosis (CF) cohort diagnosed by newborn screening and followed up to month 24. METHODS: A prospective longitudinal multicenter study assessing nutritional status according to pancreatic status, feeding modalities, prescriptions, pulmonary outcome, and biological nutritional parameters. RESULTS: One hundred and five infants were recruited and 99 completed the study. Nutritional care management prevented undernutrition and stunting in those with exocrine pancreatic sufficiency (EPS), but affected (13/87) 15% and (21/86) 24%, respectively, of infants with exocrine pancreatic insufficiency (EPI). The logistic regression model found a positive association between both weight and length z scores "at risk" at month 24, and initial pulmonary symptoms (odds ratio [OR] 0.06, P < 0.01 and OR 0.08, P < 0.01, respectively); these symptoms were less frequent when age at first visit was earlier than 1.2 months (33% vs 67%, P = 0.02); stunting was also associated with high-calorie density intake and Staphylococcus aureus (OR 0.05, P = 0.01 and OR 0.17, P < 0.01). Pulmonary outcome did not differ according to pancreatic status; breast-feeding for at least 3 months delayed first acquisition of Pseudomonas aeruginosa. Despite sodium and fat-soluble vitamin supplementation, half of both cohorts had low urinary sodium output and half of the EPI cohort had low vitamin D levels. CONCLUSIONS: Our data shed light on the fact that stunting was more frequent than undernutrition, while both parameters involved only patients with pancreatic insufficiency. Modalities of feeding were not associated with nutritional status; breast-feeding may provide some protection against acquisition of P aeruginosa.

Hyperthyrotropinemia in newly diagnosed cystic fibrosis patients with pancreatic insufficiency reversed by enzyme therapy.

Patients with cystic fibrosis (CF) commonly present with an elevated TSH concentration, suggesting subclinical hypothyroidism. Its relation to concomitant pancreatic insufficiency and its natural course upon initiation of enzyme replacement have not been adequately studied. Herein, we investigated the thyroid function in newly diagnosed infants with CF and monitored the course of thyroid function response to pancreatic enzyme substitution treatment. Fourteen, newly diagnosed infants with CF and pancreatic insufficiency, were followed every 6-8 weeks for 6 months ensuing onset of pancreatic enzyme substitution therapy. All infants had normal TSH values on neonatal screening. Ten out of 14 (71%) had hyperthyrotropinemia and normal freeT4 values at presentation. No patient received thyroxine. Upon follow-up, after 6 months, TSH values normalized in 90% of infants with CF and hyperthyrotropinemia. Serum selenium levels were negatively correlated with TSH levels. CONCLUSION: Mild TSH elevation is a frequent finding in newly diagnosed cystic fibrosis patients with pancreatic insufficiency during infancy. TSH elevation resolves in most cases after initiation of enzyme substitution and improvement of nutritional status without any substitutive therapy with thyroxine. What is Known: • Newly diagnosed infants with cystic fibrosis often present with a state of hyperthyrotropinemia suggesting subclinical hypothyroidism. What is New: • Pancreatic enzyme substitution and improvement of nutrition restores normal TSH levels without the need of thyroxine therapy.

Controversias sobre el rastreo de los niveles séricos de vitamina D y su suplementación / Controversies about serum vitamin D levels screening and its supplementation

Si bien los niveles bajos de vitamina D se han asociado con varios resultados de interés en salud, aún resulta motivo de controversia qué significa un nivel bajo, cual es la utilidad de su suplementación y cuales son sus potenciales efectos adversos. En ese contexto, se realizó en el Servicio de Medicina Familiar y Comunitaria del Hospital Italiano un taller de discusión denominado "Actividad ECCO" (Evidencia Científica en la Clínica Cotidiana) en la que fueron presentados los resulta-dos de estudios identificados que hubieran comparado el uso de vitamina D (con o sin suplementación de calcio) ver-sus placebo, con el objetivo de discutir cuál es la evidencia actual para el rastreo de deficiencia de vitamina D y para, eventualmente, recomendar o no su suplementación. Este artículo resume la evidencia identificada y las conclusiones consensuadas en dicha actividad. (AU)

Although low levels of vitamin D have been associated with several health outcomes, it is controversial what a low level means, the usefulness of its supplementation and its potential adverse effects. In this context, a workshop called "ECCO Activity" (Scientific Evidence in the Daily Clinic) was held in the Family and Community Medicine Division of Hospital Italiano de Buenos Aires, where the results of identified studies that compared the use of vitamin D (with or without calcium supplementation) versus placebo, with the aim of discussing what is the current evidence for screening of vitamin D deficiency and to, eventually, recommend or not its supplementation. This article summarizes the identified evidence and the agreed conclusions in that activity. (AU)

Choline supplementation alters some amino acid concentrations with no change in homocysteine in children with cystic fibrosis and pancreatic insufficiency.

The present study determined the plasma amino acid status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI) in the modern medical and nutritional care setting and investigated the effect of choline supplementation on amino acid status. A total of 110 children aged 5 to 18 years with CF and PI were randomized to receive choline-enriched structured lipid (LYM-X-SORB) or placebo with similar energy and fat content. Plasma amino acids were measured at baseline and 3 and 12 months. We hypothesized that choline supplementation would result in lower plasma homocysteine concentrations in children with CF. At baseline, dietary protein intake was high and the amino acid profile was within laboratory reference ranges in most participants. Alanine and cysteine were elevated in 24% and 36% of participants, respectively. Children with baseline alanine above reference range had improved weight, body mass index, and fat-free mass. Low homocysteine was found in 62% of children 11 years and older. After 3 and 12 months, there was no effect of choline supplementation on methionine or homocysteine status. Compared with placebo, choline supplementation resulted in increased glycine and decreased threonine, histidine, valine, and total branch chained amino acids at 12 months. In conclusion, daily choline supplementation with LYM-X-SORB did not alter methionine-homocysteine metabolism but did result in alterations in other amino acids in children with CF and PI.

Effect of Oral Lipid Matrix Supplement on Fat Absorption in Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

Pancreatic enzyme therapy does not normalize dietary fat absorption in patients with cystic fibrosis and pancreatic insufficiency. Efficacy of LYM-X-SORB (LXS), an easily absorbable lipid matrix that enhances fat absorption, was evaluated in a 12-month randomized, double-blinded, placebo-controlled trial with plasma fatty acids (FA) and coefficient of fat absorption (CFA) outcomes. A total of 110 subjects (age 10.4 ±â€Š3.0 years) were randomized. Total FA increased with LXS at 3 and 12 months (+1.58, +1.14 mmol/L) and not with placebo (P = 0.046). With LXS, linoleic acid (LA) increased at 3 and 12 months (+298, +175 nmol/mL, P ≤ 0.046), with a 6% increase in CFA (P < 0.01). LA increase was significant in LXS versus placebo (445 vs 42 nmol/mL, P = 0.038). Increased FA and LA predicted increased body mass index Z scores. In summary, the LXS treatment improved dietary fat absorption compared with placebo as indicated by plasma FA and LA and was associated with better growth status.

A randomized controlled trial of vitamin D replacement strategies in pediatric CF patients.

BACKGROUND: Vitamin D insufficiency is common in children with cystic fibrosis (CF), yet data are sparse regarding the most effective form of vitamin D supplementation. The aim of this study was to compare two different vitamin D replacement regimens. METHODS: We conducted a randomized controlled trial comparing 50,000 IU of ergocalciferol (vitamin D2) twice weekly for 8 weeks versus 50,000 IU of cholecalciferol (vitamin D3) weekly in patients with CF, pancreatic insufficiency, age 6-21 years and a 25(OH)D<30 ng/mL. The primary outcome was change in serum 25(OH)D concentration. For secondary analyses, we examined changes in IgG, IgE and CRP in patients who normalized their vitamin D levels. RESULTS: A total of 47 patients completed the trial. The mean pre-treatment 25(OH)D concentration was 23.1 (SD 4.7) ng/mL. The overall mean increase in 25(OH)D was 11.1 (11.9) ng/mL and 31/47 (66%) achieved a 25(OH)D concentration ≥ 30 ng/mL; of the 26 participants who received D2, 18 (69%) achieved sufficiency while 13/21 (62%) participants treated with D3 achieved sufficiency. There was no difference between groups in change of 25(OH)D (p=0.65). Similarly, there was no difference in the number of patients to achieve vitamin D sufficiency between treatments (p=0.6). CONCLUSIONS: Ergocalciferol administered as 50,000 IU twice weekly is as effective as cholecalciferol 50,000 IU weekly for 8 weeks in pediatric patients with CF and vitamin D insufficiency. Only 66% of the patients studied achieved the desired 25(OH)D concentration.

Nutritional status in children with Shwachman-diamond syndrome.

OBJECTIVE: In Shwachman-Diamond syndrome (SDS), pancreatic insufficiency can lead to malabsorption of fat-soluble vitamins and trace elements. The aim of this study was to assess the serum concentrations of vitamins A and E, zinc, copper, and selenium and their deficiencies. METHODS: This retrospective review was performed in 21 children (12 were male; median age, 7.8 years) with genetically confirmed SDS at a tertiary pediatric hospital. Pancreatic enzyme replacement therapy (PERT) and vitamin or trace elements supplements were documented. RESULTS: Twenty patients (95%) had pancreatic insufficiency receiving PERT, 10 (47%) had a combined vitamin and trace element deficiency, 6 (29%) had an isolated vitamin deficiency, and 4 (19%) had an isolated trace element deficiency. Vitamins A and E deficiency occurred in 16 (76%) and 4 (19%) of 21, respectively. Low serum selenium was found in 10 (47%), zinc deficiency in 7 (33%), and copper deficiency in 5 (24%). Eleven patients (52%) were on multivitamin supplementation, and 2 (10%) on zinc and selenium supplements. No statistical differences were found between repeated measurements for all micronutrients. CONCLUSIONS: More than 50% of the children had vitamin A and selenium deficiencies despite adequate supplementation of PERT and supplements. Micronutrients should be routinely measured in SDS patients to prevent significant complications.

[Fat-soluble vitamins supplementation in patients with cystic fibrosis: is enough Aquadek's®?]. / Suplementacion con vitaminas liposolubles en pacientes con fibrosis quistica: ¿es suficiente con Aquadek's®?

INTRODUCTION AND OBJECTIVE: Evaluate the safety and efficacy of a novel polyvitaminic (Aquadek's®) in patients with Cystic Fibrosis (CF). MATERIAL AND METHODS: Prospective, longitudinal and non-randomized study. CF patients with pancreatic insufficiency and clinically stable were given Aquadek's® (two chewable tablets) daily for 12 months. Serum levels of retinol, beta-carotene, 25 OH vitamin D and α-tocopherol were evaluated twelve months before, at baseline and 12 months after. STATISTICAL ANALYSIS: paired t tests. RESULTS: 28 patients aged 6 to 39 years (median 18.5 years) were included. Aquadek's® supplementation led to an increase in vitamin A dose and a decrease in the number of tablets administered. At baseline, 89% had at least one vitamin deficiency (61% pro-Vitamin A and 54% vitamin D). After one year, serum beta-carotene levels were increases 160 (95% CI 98-222) mcg/l (p <0.001) and decreased the percentage of patients with pro-vitamin A deficiency 46% (95% CI 22-64) (p <0.001). The proportion of patients with vitamin D insuficiency increased 18%(95% CI 2-32) (p =0.025). In any case serum levels exceeded the upper limits used to assess the risk of toxicity.Conclusions: Two daily Aquadek's® chewable tablets are safe and effective for maintaining vitamin A and E status of CF patients older than 6 years, although it is insufficient to normalize serum 25OHvitaminD according to the current recommendations for this disease.

Introducción y objetivo: Conocer si la suplementación un nuevo polivitamínico (Aquadek´s®) durante 12 meses es segura y eficaz en pacientes con Fibrosis Quística (FQ). Material y Métodos: Estudio prospectivo, longitudinal y no controlado en pacientes con FQ insuficientes pancreáticos, clínicamente estables, que recibieron suplementación con Aquadek´s® (2 comprimidos masticables) durante 12 meses en lugar de su suplementación habitual. Se evaluaron niveles séricos de retinol, betacarotenos, 25 OH vitamina D y α-tocoferol un año antes, al inicio y tras un año de tratamiento. Análisis estadístico: Pruebas t para datos pareados. Resultados: Se incluyeron 28 pacientes entre 6 y 39 años (mediana 18,5 años). La suplementación con Aquadek´s® supuso un incremento en la dosis de vitaminas A y una disminución del número de comprimidos administrados. Al inicio, un 89% presentaban algún tipo de déficit vitamínico: (61% pro-Vitamina A y 54% vitamina D). Tras un año, se produjo un incremento de los niveles de betacarotenos: 160 mcg/l (IC 95% 98-222) (p.

Vitamin D supplementation for cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a genetic disorder with multiorgan effects. In a subgroup with pancreatic insufficiency malabsorption of the fat soluble vitamins (A, D, E, K) may occur. Vitamin D is involved in calcium homeostasis and bone mineralisation and may have extraskeletal effects. This review examines the evidence for vitamin D supplementation in cystic fibrosis. OBJECTIVES: To assess the effects of vitamin D supplementation on the frequency of vitamin D deficiency, respiratory outcomes and vitamin D toxicity in the cystic fibrosis population. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 08 July 2013. SELECTION CRITERIA: Randomised and quasi-randomised controlled studies of vitamin D supplementation compared to placebo in the cystic fibrosis population regardless of exocrine pancreatic function. DATA COLLECTION AND ANALYSIS: Both authors independently assessed the risk of bias of each included study and extracted outcome data (from published study information) for assessment of bone mineralization, growth and nutritional status, frequency of vitamin D deficiency, respiratory status, quality of life and adverse events. MAIN RESULTS: Six studies (239 participants) are included, although only three studies provided data from 69 adults and children with cystic fibrosis for analysis. One study compared a single high dose of vitamin D (250,000 IU) to placebo at the time of hospital admission with a respiratory exacerbation in 30 pancreatic insufficient adults with cystic fibrosis. The second study compared supplemental 800 international units (IU) vitamin D and placebo for 12 months in 30 osteopenic pancreatic insufficient adults; both groups continued 900 IU vitamin D daily. The third study compared supplemental 1 g calcium alone, 1600 IU vitamin D alone, 1600 IU vitamin D and 1 g calcium and placebo in a double-blind randomised cross-over study; only nine children who completed both vitamin D and placebo groups after six-months supplementation and a three-month washout period are included; pancreatic sufficiency or disease status of participants are not defined. The studies are not directly comparable due to differences in supplementation, outcome reporting and possibly participant characteristics (e.g. severity of lung disease, growth and nutrition, pancreatic sufficiency).The only outcome for which we could combine data from more than two studies was 25-hydroxyvitamin D levels; patients receiving vitamin D supplementation had significantly higher levels, mean difference 7.24 ng/ml (95% confidence interval 5.01 to 9.46). However, ironically one study reported 1,25(OH)2D with levels significantly favouring the placebo group, mean difference -30.30 pmol/ml (95% confidence interval -59.89 to -0.71). Bone mineral density was measured in two studies; both described no significant change between groups. There were no adverse events in any study.The remaining three studies are published as abstracts only and did not provide data for analysis. These abstracts include: a report of pre-intervention data in a study comparing daily calcitriol (0.25 or 0.5 micrograms) with placebo in pancreatic insufficient children and young adults; an interim report of a double-blind randomised control study comparing 5000 IU vitamin D daily for 12 weeks during winter in 67 adult cystic fibrosis patients; and a comparison of the effect of three months of vitamin D supplementation (dose not specified) with placebo on bone mineral density in 42 children with cystic fibrosis and low bone mineral density.Risk of bias was highly variable between all studies. Only one study had a low risk of bias for the five main criteria (random sequence generation, allocation, blinding, attrition and reporting). The rest of the studies had unclear or high risks of bias. Two studies had a low risk of bias for blinding and another two studies for attrition bias. In the studies published as abstracts, assessment of the risks of bias was uncertain in many aspects. AUTHORS' CONCLUSIONS: In patients receiving vitamin D supplementation, 25-hydroxyvitamin D levels are significantly higher. However, there is no evidence of clinical benefit or harm in the limited number of small-sized published studies. Adherence to relevant cystic fibrosis guidelines on vitamin D supplementation should be considered until further evidence is available.

Fat-soluble vitamins in cystic fibrosis and pancreatic insufficiency: efficacy of a nutrition intervention.

OBJECTIVES: The aim of the study was to assess the impact of LYM-X-SORB (LXS), an organized lipid matrix that has been shown to be absorbable without pancreatic enzyme therapy on fat-soluble vitamin status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI). METHODS: Children with CF and PI were randomized to daily LXS or an isocaloric placebo comparison supplement for 12 months. Serum vitamins A (retinol), D (25-hydroxyvitamin D[25D]), E (α-tocopherol, α-tocopherol:cholesterol ratio), and K (percentage of undercarboxylated osteocalcin [%ucOC] and plasma proteins induced by vitamin K absence factor II [PIVKA II]) were assessed at baseline and 12 months. Dietary intake was determined using 3-day weighed food records and supplemental vitamin intake by a comprehensive questionnaire. RESULTS: A total of 58 subjects (32 boys, age 10.3 ± 2.9 years [mean ± standard deviation]) with complete serum vitamin, dietary and supplemental vitamin data were analyzed. After adjusting for dietary and supplemental vitamin intake, serum retinol increased 3.0 ± 1.4 µg/dL (coefficient ± standard error) (adjusted R2 = 0.02, P = 0.03) and vitamin K status improved as demonstrated by a decreased percentage of undercarboxylated osteocalcin of -6.0% ± 1.6% by 12 months (adjusted R2 = 0.15, P < 0.001). These changes occurred in both the LXS and placebo comparison groups. No changes in serum 25D or α-tocopherol were detected. Both nutrition interventions increased caloric intake a mean of 83 ± 666 kcal/day by 12 months. CONCLUSIONS: Vitamins A and K status improved, whereas vitamins D and E status was unchanged during 12 months of LXS and isocaloric placebo comparison supplement in children with CF and PI.