Fat-Soluble Vitamins in Standard vs. Liposomal Form Enriched with Vitamin K2 in Cystic Fibrosis: A Randomized Multi-Center Trial.

BACKGROUND: We aimed to assess a liposomal fat-soluble vitamin formulation containing vitamin K2 with standard treatment in cystic fibrosis (CF). METHODS: A multi-center randomized controlled trial was carried out in 100 pancreatic-insufficient patients with CF. The liposomal formulation contained vitamin A as retinyl palmitate (2667 IU daily) and beta-carotene (1333 IU), D3 (4000 IU), E (150 IU), K1 (2 mg), and K2 as menaquinone-7 (400 µg). It was compared with the standard vitamin preparations in the closest possible doses (2500 IU, 1428 IU, 4000 IU, 150 IU, 2.14 mg, respectively; no vitamin K2) over 3 months. RESULTS: Forty-two patients finished the trial in the liposomal and 49 in the control group (overall 91 pts: 22.6 ± 7.6 years, 62.6% female, BMI 19.9 ± 2.8 kg/m2, FEV1% 70% ± 30%). The main outcome was the change of vitamin status in the serum during the study (liposomal vs. standard): all-trans-retinol (+1.48 ± 95.9 vs. -43.1 ± 121.4 ng/mL, p = 0.054), 25-hydroxyvitamin D3 (+9.7 ± 13.4 vs. +2.0 ± 9.8 ng/mL, p = 0.004), α-tocopherol (+1.5 ± 2.5 vs. -0.2 ± 1.6 µg/mL, p < 0.001), %undercarboxylated osteocalcin (-17.2 ± 24.8% vs. -8.3 ± 18.5%, p = 0.061). The secondary outcome was the vitamin status at the trial end: all-trans-retinol (370.0 ± 116.5 vs. 323.1 ± 100.6 ng/mL, p = 0.045), 25-hydroxyvitamin D3 (43.2 ± 16.6 vs. 32.7 ± 11.5 ng/mL, p < 0.001), α-tocopherol (9.0 ± 3.1 vs. 7.7 ± 3.0 µg/mL, p = 0.037), %undercarboxylated osteocalcin (13.0 ± 11.2% vs. 22.7 ± 22.0%, p = 0.008). CONCLUSION: The liposomal fat-soluble vitamin supplement containing vitamin K2 was superior to the standard form in delivering vitamin D3 and E in pancreatic-insufficient patients with CF. The supplement was also more effective in strengthening vitamin K-dependent carboxylation, and could improve vitamin A status.

Fat-Soluble Vitamin Supplementation Using Liposomes, Cyclodextrins, or Medium-Chain Triglycerides in Cystic Fibrosis: A Randomized Controlled Trial.

Fat-soluble vitamin deficiency remains a challenge in cystic fibrosis (CF), chronic pancreatitis, and biliary atresia. Liposomes and cyclodextrins can enhance their bioavailability, thus this multi-center randomized placebo-controlled trial compared three-month supplementation of fat-soluble vitamins in the form of liposomes or cyclodextrins to medium-chain triglycerides (MCT) in pancreatic-insufficient CF patients. The daily doses were as follows: 2000 IU of retinyl palmitate, 4000 IU of vitamin D3, 200 IU of RRR-α-tocopherol, and 200 µg of vitamin K2 as menaquinone-7, with vitamin E given in soybean oil instead of liposomes. All participants received 4 mg of ß-carotene and 1.07 mg of vitamin K1 to ensure compliance with the guidelines. The primary outcome was the change from the baseline of all-trans-retinol and 25-hydroxyvitamin D3 concentrations and the percentage of undercarboxylated osteocalcin. Out of 75 randomized patients (n = 28 liposomes, n = 22 cyclodextrins, and n = 25 MCT), 67 completed the trial (89%; n = 26 liposomes, n = 18 cyclodextrins, and n = 23 MCT) and had a median age of 22 years (IQR 19-28), body mass index of 20.6 kg/m2 [18.4-22.0], and forced expiratory volume in 1 s of 65% (44-84%). The liposomal formulation of vitamin A was associated with the improved evolution of serum all-trans-retinol compared to the control (median +1.7 ng/mL (IQR -44.3-86.1) vs. -38.8 ng/mL (-71.2-6.8), p = 0.028). Cyclodextrins enhanced the bioavailability of vitamin D3 (+9.0 ng/mL (1.0-17.0) vs. +3.0 ng/mL (-4.0-7.0), p = 0.012) and vitamin E (+4.34 µg/mL (0.33-6.52) vs. -0.34 µg/mL (-1.71-2.15), p = 0.010). Liposomes may augment the bioavailability of vitamin A and cyclodextrins may strengthen the supplementation of vitamins D3 and E relative to MCT in pancreatic-insufficient CF but further studies are required to assess liposomal vitamin E (German Clinical Trial Register number DRKS00014295, funded from EU and Norsa Pharma).

Comparison of the Effect of Amaranth Oil vs. Rapeseed Oil on Selected Atherosclerosis Markers in Overweight and Obese Subjects: A Randomized Double-Blind Cross-Over Trial.

It is well known that rapeseed oil improves lipid profile and has antiatherosclerotic properties. Recently, amaranth oil has also become popular due to its potential health benefits. However, the effect of this oil on atherosclerosis markers in humans is not clear. Therefore, this study aimed to compare the effect of amaranth and rapeseed oils on selected atherosclerosis-related parameters in overweight and obese subjects. In this randomized cross-over study, 44 subjects were instructed to consume 20 mL of amaranth oil and rapeseed oil during two consecutive three-week intervention periods separated by a washout period of the same duration as the intervention. The outcome variables included changes in tumor necrosis factor-alpha, adiponectin, oxidized low-density lipoprotein, apolipoproteins (Apo) A1, B and E as well as glucose and insulin homeostasis markers. Compared to rapeseed oil, amaranth oil had a slight positive effect on adiponectin levels (mean (95% confidence interval): 0.55 (0.22-0.89) vs. -0.29 (-0.75-0.16), p = 0.0002) but negatively affected ApoB concentrations (0.05 (-0.01-0.11) vs. 0.03 (-0.07-0.00), p = 0.0004) and ApoB/A1 ratio (0.01 (-0.03-0.05) vs. -0.02 (-0.04-0.00), p = 0.0113). No differences between the other analyzed parameters were observed. In conclusion, amaranth oil does not have a greater beneficial effect on atherosclerosis markers than rapeseed oil. However, further studies with a longer intervention period are needed. The study was retrospectively registered with the German Clinical Trials Register within the number: DRKS00014046, date of registration: 3 May 2018.

Amaranth Oil Increases Total and LDL Cholesterol Levels without Influencing Early Markers of Atherosclerosis in an Overweight and Obese Population: A Randomized Double-Blind Cross-Over Study in Comparison with Rapeseed Oil Supplementation.

BACKGROUND: Atherosclerosis (AT) is a chronic inflammatory process in which oxidative stress is the key event. Amaranth oil (AmO) has potential hypolipidemic and antiatherogenic effects. The aim of the study was to compare the effects of AmO and rapeseed oil (RaO) supplementation on expression of early markers of AT and lipid profile in obese or overweight subjects. METHODS: A randomized, double-blinded cross-over study was conducted, in which participants took 20 mL of AmO in the first arm and 20 mL RaO in the second arm, switching after the washout period. Serum concentrations of adhesion molecules (sP-selectin, sVCAM-1), high-sensitivity C-reactive protein (hsCRP), asymmetric dimethylarginine (ADMA), and lipid profile were assessed before and after nutritional interventions. In addition, anthropometric parameters were measured. RESULTS: The total (TC) and low-density lipoprotein (LDL) cholesterol concentrations increased significantly in the AmO group in comparison with RaO (ΔTC 5.52 ± 35 vs. -8.43 ± 17.65 mg/dL; p = 0.002 and 4.43 ± 34.96 vs. -7.55 ± 16.41 mg/dL; p = 0.002, respectively). There were no significant differences in other parameters analyzed between the groups. CONCLUSION: The use of AmO instead of RaO may increase cardiovascular risk in obese and overweight subjects.

Vitamin E status and its determinants in patients with cystic fibrosis.

PURPOSE: The risk of vitamin E deficiency is of primary concern in cystic fibrosis patients. However, early diagnosis and routine vitamin E supplementation can lead to its normal or even high levels. In the present study, we assessed vitamin E status in a large group of cystic fibrosis patients. Moreover, we also aimed to establish determinants of its body resources in cystic fibrosis patients. MATERIAL AND METHODS: The study group comprised 211 cystic fibrosis patients aged from 1 month to 48 years. In all of them serum α-tocopherol concentration was analyzed using high-performance liquid chromatography. RESULTS: Median vitamin E concentration was 9.9 µg/ml (1st-3rd quartile: 7.5-13.5). Vitamin E deficiency was found in 17 (8.0%) and high levels were documented in 24 (11.4%) participants. Patients with and without vitamin E deficiency did not differ significantly with respect to age, standardized body weight and height, FEV1, albumin concentration and vitamin E supplementation dose. However, vitamin E deficiency appeared more frequently in participants without vitamin E supplementation. Moreover, in multiple linear regression analysis pancreatic insufficiency, severe CFTR gene mutation and vitamin E dose, were potentially defined as determinants of vitamin E concentration. CONCLUSIONS: Vitamin E deficiency in cystic fibrosis patients is rather rare nowadays. Excessive vitamin E levels seem to be more frequent. Vitamin E status wasn't documented to be strictly related to clinical determinants. Beyond vitamin E supplementation, exocrine pancreatic function and CFTR gene mutations may have had an impact on the vitamin E body resources in cystic fibrosis patients.