CFTR Modulator Therapy with Lumacaftor/Ivacaftor Alters Plasma Concentrations of Lipid-Soluble Vitamins A and E in Patients with Cystic Fibrosis

Rationale: Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leads to impaired pancreatic function and therefore reduced intestinal absorption of lipids and fat-soluble vitamins especially in patients with CF developing pancreatic insufficiency (PI). Previous studies showed that CFTR modulator therapy with lumacaftor-ivacaftor (LUM/IVA) in Phe508del-homozygous patients with CF results in improvement of pulmonary disease and thriving. However, the effects of LUM/IVA on plasma concentration of the lipid soluble vitamins A and E remain unknown. Objectives: To investigate the course of plasma vitamin A and E in patients with CF under LUM/IVA therapy. Methods: Data from annual follow-up examinations of patients with CF were obtained to assess clinical outcomes including pulmonary function status, body mass index (BMI), and clinical chemistry as well as fat-soluble vitamins in Phe508del-homozygous CF patients before initiation and during LUM/IVA therapy. Results: Patients with CF receiving LUM/IVA improved substantially, including improvement in pulmonary inflammation, associated with a decrease in blood immunoglobulin G (IgG) from 9.4 to 8.2 g/L after two years (p < 0.001). During the same time, plasma vitamin A increased significantly from 1.2 to 1.6 µmol/L (p < 0.05), however, levels above the upper limit of normal were not detected in any of the patients. In contrast, plasma vitamin E as vitamin E/cholesterol ratio decreased moderately over the same time from 6.2 to 5.5 µmol/L (p < 0.01). Conclusions: CFTR modulator therapy with LUM/IVA alters concentrations of vitamins A and vitamin E in plasma. The increase of vitamin A must be monitored critically to avoid hypervitaminosis A in patients with CF.

Download Full-text

Antioxidant Role of Plasma Carotenoids in Bronchopulmonary Dysplasia in Preterm Infants

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.79.56.288 ◽

2009 ◽

Vol 79 (56) ◽

pp. 288-296 ◽

Cited By ~ 8

Author(s):

Annelies Vogelsang ◽

Richard A. van Lingen ◽

Janine Slootstra ◽

Bert D. Dikkeschei ◽

Boudewijn J. Kollen ◽

...

Keyword(s):

Vitamin E ◽

Vitamin A ◽

Preterm Infants ◽

Bronchopulmonary Dysplasia ◽

Plasma Concentrations ◽

Antioxidant Defenses ◽

Control Group ◽

Cholesterol Ratio ◽

Β Carotene

Objectives: Oxidative stress is implicated in the pathogenesis of bronchopulmonary dysplasia (BPD) and consequently, it might be theorized that sufficient antioxidant defenses are needed to prevent BPD. We hypothesized that, except for vitamins E and A, carotenoids may be important in this defense. Carotenoids are present in human milk; however, they are not added to parenteral nutrition, the main food source of preterm infants in the first week of life. Aim: To evaluate prospectively the role of carotenoids in BPD in a cohort of preterm infants. Methods: The plasma concentrations of F2α-isoprostane, α- and β-carotene, lycopene, lutein, vitamin A, and the vitamin E/cholesterol ratio were studied at days 1, 3, and 7 in a cohort of 109 preterm infants, of whom 19 had BPD. Results: When comparing the BPD and control group, infants in the BPD group were younger (p<0.001) and β-carotene (day 7, p<0.01) and vitamin A concentrations were lower (days 3 and 7, p<0.001). Lycopene, lutein, α-carotene, vitamin E, and F2α-isoprostane concentrations did not differ between groups. Conclusions: Plasma β-carotene and vitamin A concentrations are lower in BPD infants which may result in a reduction of their antioxidant protection.

Download Full-text

Effect of vitamin E intake from food and supplement sources on plasma α- and γ-tocopherol concentrations in a healthy Irish adult population

British Journal Of Nutrition ◽

10.1017/s0007114514002438 ◽

2014 ◽

Vol 112 (9) ◽

pp. 1575-1585 ◽

Cited By ~ 20

Author(s):

Yang Zhao ◽

Frank J. Monahan ◽

Breige A. McNulty ◽

Mike J. Gibney ◽

Eileen R. Gibney

Keyword(s):

Vitamin E ◽

Adult Population ◽

Plasma Concentrations ◽

Fats And Oils ◽

Food Sources ◽

Dietary Vitamin ◽

Plasma Vitamin ◽

Institute Of Medicine ◽

Nutrition Survey ◽

Plasma Vitamin E

Vitamin E is believed to play a preventive role in diseases associated with oxidative stress. The aims of the present study were to quantify vitamin E intake levels and plasma concentrations and to assess dietary vitamin E adequacy in Irish adults. Intake data from the National Adult Nutrition Survey were used; plasma samples were obtained from a representative cohort of survey participants. Plasma α- and γ-tocopherol concentrations were measured by HPLC. The main sources of vitamin E in the diet were ‘butter, spreadable fats and oils’ and ‘vegetables and vegetable dishes’. When vitamin E intake from supplements was taken into account, supplements were found to be the main contributor, making a contribution of 29·2 % to vitamin E intake in the total population. Supplement consumers had significantly higher plasma α-tocopherol concentrations and lower plasma γ-tocopherol concentrations when compared with non-consumers. Consumers of ‘vitamin E’ supplements had significantly higher vitamin E intake levels and plasma α-tocopherol concentrations compared with consumers of other types of supplements, such as multivitamin and fish oil. Comparison with the Institute of Medicine Estimated Average Requirement of 12 mg/d indicated that when vitamin E intake from food and supplement sources was taken into account, 100 % of the study participants achieved the recommended intake levels. When vitamin E intake from food sources was taken into account, only 68·4 % of the females were found to achieve the recommended intake levels compared with 99·2 % of the males. The results of the present study show that dietary vitamin E intake has a significant effect on plasma α- and γ-tocopherol concentrations. Furthermore, they show that the consumption of supplements is a major contributor to overall intake and has a significant effect on plasma vitamin E concentrations in the Irish population.

Download Full-text

VITAMIN A POISONING

PEDIATRICS ◽

10.1542/peds.7.3.372 ◽

1951 ◽

Vol 7 (3) ◽

pp. 372-385

Author(s):

DONALD GRIBETZ ◽

SAMUEL H. SILVERMAN ◽

ALBERT E. SOBEL

Keyword(s):

Vitamin A ◽

Experimental Studies ◽

Plasma Vitamin ◽

Hypervitaminosis A ◽

Total Vitamin ◽

Toxic Factor ◽

Vitamin Intake ◽

First Case ◽

Alcohol Fraction ◽

Clinical Literature

Two cases of hypervitaminosis A have been presented together with a review of experimental and clinical literature. The first case presented the highest reported fasting plasma vitamin A level, the increase being chiefly due to a high vitamin A alcohol fraction. This elevated level of alcoholic vitamin A probably denotes large stores of vitamin A in the liver and data have been given to show that it is a better index of hypervitaminosis A than is the total vitamin A level. In addition, evidence has been presented that the toxic factor in hypervitaminosis A is the permanent elevated plasma vitamin A level. The similarity between the experimental studies in animals and the observations in the authors' first case has been shown. The important points necessary for making a diagnosis of hypervitaminosis A have been discussed and several similar conditions have been differentiated. It cannot be emphasized too strongly that excess vitamin intake may be as dangerous as a deficient intake.

Download Full-text

Impact of storage conditions and premix type on fat-soluble vitamin stability1

Translational Animal Science ◽

10.1093/tas/txaa143 ◽

2020 ◽

Vol 4 (3) ◽

Author(s):

Marut Saensukjaroenphon ◽

Caitlin E Evans ◽

Chad B Paulk ◽

Jordan T Gebhardt ◽

Jason C Woodworth ◽

...

Keyword(s):

Vitamin E ◽

Vitamin A ◽

Chemical Treatment ◽

Storage Time ◽

Storage Condition ◽

The United States ◽

Heat Pulse ◽

Pulse Treatment ◽

Fat Soluble Vitamins ◽

And Storage

Abstract Feed ingredients and additives could be a potential medium for foreign animal disease entry into the United States. The feed industry has taken active steps to reduce the risk of pathogen entry through ingredients. Medium chain fatty acid (MCFA) and heat pulse treatment could be an opportunity to prevent pathogen contamination. The objective of experiment 1 was to determine the impact of 0, 30, 60, or 90 d storage time on fat-soluble vitamin stability when vitamin premix (VP) and vitamin trace mineral premix (VTM) were blended with 1% inclusion of MCFA (1:1:1 blend of C6:C8:C10) or mineral oil (MO) with different environmental conditions. Samples stored at room temperature (RT) (~22 °C) or in an environmentally controlled chamber set at 40 °C and 75% humidity, high-temperature high humidity (HTHH). The sample bags were pulled out at days 0, 30, 60 and 90 for RT condition and HTHH condition. The objective of experiment 2 was to determine the effect of heat pulse treatment and MCFA addition on fat-soluble vitamin stability with two premix types. A sample from each treatment was heated at 60 °C and 20% humidity. For experiment 1, the following effects were significant for vitamin A: premix type × storage condition (P = 0.031) and storage time × storage condition (P = 0.002) interactions; for vitamin D3: main effect of storage condition (P < 0.001) and storage time (P = 0.002); and for vitamin E: storage time × storage condition interaction (P < 0.001). For experiment 2, oil type did not affect the stability of fat-soluble vitamins (P > 0.732) except for vitamin A (P = 0.030). There were no differences for fat-soluble vitamin stability between VP and VTM (P > 0.074) except for vitamin E (P = 0.016). Therefore, the fat-soluble vitamins were stable when mixed with both vitamin and VTM and stored at 22 °C with 28.4% relative humidity (RH). When premixes were stored at 39.5 °C with 78.8%RH, the vitamin A and D3 were stable up to 30 d while the vitamin E was stable up to 60 d. In addition, MCFA did not influence fat-soluble vitamin degradation during storage up to 90 d and in the heat pulse process. The vitamin stability was decreased by 5% to 10% after the premixes was heated at 60 °C for approximately nine and a half hours. If both chemical treatment (MCFA) and heat pulse treatment have similar efficiency at neutralizing or reducing the target pathogen, the process of chemical treatment could become a more practical practice.

Download Full-text

Depressed plasma Vitamin A and retinol-binding protein in cystic fibrosis correlations with zinc deficiency

American Journal of Clinical Nutrition ◽

10.1093/ajcn/34.7.1439 ◽

1981 ◽

Vol 34 (7) ◽

pp. 1439-1440 ◽

Cited By ~ 11

Author(s):

J Navarro ◽

N Desquilbet

Keyword(s):

Cystic Fibrosis ◽

Vitamin A ◽

Zinc Deficiency ◽

Binding Protein ◽

Retinol Binding Protein ◽

Plasma Vitamin

Download Full-text

The growing pancreatic duct ligated pig as a model for exocrine pancreatic insufficiency in children: Investigations to achieve sufficient vitamin A and vitamin E supply

Journal of Animal Science ◽

10.2527/jas.53775 ◽

2012 ◽

Vol 90 (suppl_4) ◽

pp. 321-323 ◽

Cited By ~ 5

Author(s):

A. Mößeler ◽

T. Schwarzmaier ◽

J. Grunemann ◽

P. C. Gregory ◽

M. Höltershinken ◽

...

Keyword(s):

Vitamin E ◽

Vitamin A ◽

Pancreatic Duct ◽

Pancreatic Insufficiency ◽

Exocrine Pancreatic Insufficiency ◽

Sufficient Vitamin

Download Full-text

Fat-Soluble Vitamins in Human Lactation

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.77.5.303 ◽

2007 ◽

Vol 77 (5) ◽

pp. 303-310 ◽

Cited By ~ 8

Author(s):

Campos ◽

Paixão ◽

Ferraz

Keyword(s):

Vitamin E ◽

Vitamin A ◽

Beta Carotene ◽

Group Differences ◽

Early Lactation ◽

Sharp Decline ◽

Mature Milk ◽

Human Lactation ◽

Total Fat ◽

Fat Soluble Vitamins

Lactation has three distinct phases: colostrum, transition, and mature, with the quantity of fat-soluble vitamins and carotenoids tending to decline while the total fat content increases. The number of deliveries seems to be directly related to higher concentrations of beta-carotene and vitamin E in colostrum. Little is known about vitamin quantities during the other phases. In the present study, vitamin A and E concentrations during different phases of lactation were measured in primiparous and multiparous mothers to analyze the variation and suitability for the diet of a breastfed child. Phase of lactation and number of deliveries were highly significant for log mean vitamin A while only one phase showed significance for log mean vitamin E. There was a sharp decline in the levels of vitamin A and E in the course of the initial phase of lactation. The variability between measurements declined as colostrum transitioned to mature milk. There were significant measurable inter-group differences in retinol levels in milk obtained during early lactation. Vitamin A and E content can reach 2.5 and 1.4 times of levels recommended intake, respectively.

Download Full-text