Abstract
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 β-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).
Highlights
With the advancements in cystic fibrosis (CF) care, dramatic fat-soluble vitamin deficiencies are history and current guidelines outline a mainly preventative approach to their supplementation [1]
Atioltnhoaungdh—naos pitawtieanstrsewveitahleddrelwatefrr—omditdhenloipt otaskoemtahlegproreuspc,ritbweodpeantzieynmtsesw. eArelthloosut gh notopfoatllioenwt-suwp.ithdrew from the liposomal group, two patients were lost to follow-up
Fat-soluble vitamin deficiency remains a challenge for many CF patients without access to CFTR potentiators and modulators, as well as for those who exhibit insufficient vitamin levels despite such treatment [11–14]
Summary
With the advancements in cystic fibrosis (CF) care, dramatic fat-soluble vitamin deficiencies are history and current guidelines outline a mainly preventative approach to their supplementation [1]. The use of the multivitamin A, D, E, and K tablets can augment adherence and the employment of D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) may improve vitamin E status Formulations of both approaches have become widely available over the past decade, displacing standard mono vitamin products based on medium-chain triglycerides (MCT) that are still used for therapy individualization or cost-reduction. Liposomes are nanoscale vesicles formed by amphiphilic molecules at the border of aqueous and lipophilic compartments They have been used to improve the pharmacokinetic properties of active compounds and reduce side effects, such as, for example, the FDA-approved intravenous doxorubicin [2]. A range of cyclodextrins has been used in oral and intravenous drug delivery as well as in food production under the European Union (EU) Novel Foods directive [3]
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