Corrigendum to 'Lysophosphatidylcholine-Rich Nutrition Therapy Increased Gut Absorption of Coingested Dietary Fat: a Randomized Controlled Trial' [Curr Dev Nutr. 2023 Sep; 7(9): 101985].

[This corrects the article DOI: 10.1016/j.cdnut.2023.101985.].

Lysophosphatidylcholine-Rich Nutrition Therapy Increased Gut Absorption of Coingested Dietary Fat: a Randomized Controlled Trial.

Unintentional weight loss is common in persons with chronic and acute disease and is often caused by insufficient intake or malabsorption. A new lysophosphatidylcholine (LPC)-rich structured lipid powder has micelle-like activity that facilitates digestion and absorption, independent of lipase and bile acids. The aim of this secondary analysis was to determine if recycled LPC increased fat absorption of coingested food. Fasting plasma fatty acid (FA) concentrations were measured at baseline and 3 mo in children (n = 84) with cystic fibrosis and pancreatic insufficiency. Plasma palmitic acid was selected because of its dietary prevalence and was a minor component of the LPC product. Palmitic acid increased 15% in the LPC product-treated total subjects (P = 0.01) and 23% in the subgroup with more severe malabsorption (P = 0.007), with no change in either group on placebo. Total FAs increased 11% (P = 0.009) and 20% (P = 0.005), respectively. Increased palmitic acid and total FA suggest that LPC provided by the product created an intraluminal environment that increased coingested dietary fat absorption and provided more calories. This trial was registered at clinicaltrials.gov as NCT00406536.

Changes in nutrition and growth status in young children in the first 12 weeks of ivacaftor therapy.

BACKGROUND: Highly effective CFTR modulators improve nutritional status and are of particular importance among younger children experiencing rapid growth. This study was designed to examine CFTR modulator associated changes in nutritional and other extrapulmonary outcomes in children 4-24 months of age with ivacaftor treatment over 12 weeks. METHODS: Children 4-24 months were recruited from US and Canadian CF Centers. Eligible children were ivacaftor naïve and approved to start therapy. Anthropometrics, diet, sleeping energy expenditure (SEE), nutrition biomarkers, pancreatic status, serum and fecal calprotectin, serum bile acids, plasma fatty acids were measured. Changes from baseline at 6 and 12 weeks were examined using mixed effects linear regression modeling. RESULTS: Fifteen participants enrolled (40% male). Weight-for-age z-scores increased at 6 (p = 0.03) and 12 weeks ivacaftor therapy (p<0.001) compared to baseline. Plasma docosatetraenoic acid (DTA), total saturated fatty acids increased at 6 weeks (p = 0.02) and 12 weeks (p = 0.009). At 12 weeks, serum CO2 concentration decreased (p = 0.002), serum urea nitrogen increased (p = 0.01) and fecal elastase increased (p = 0.02) compared to baseline. Bile acids, deoxycholic acid increased (p = 0.03) and ursodeoxycholic acid decreased (p = 0.02) after 12 weeks. Plasma total fatty acids, palmitic acid, mead, and docosatetraenoic acid (DTA) increased after 12 weeks (p = 0.02, p = 0.002 and p = 0.04, respectively). Plasma total saturated fatty acids increased at 6 weeks (p = 0.02) and 12 weeks (p = 0.009). Dietary intake (p = 0.04) and percent kcal from protein (p = 0.04) increased after 12 weeks compared to baseline. CONCLUSIONS: Overall, younger children experienced favorable changes in nutritional and growth status in the first 12 weeks of ivacaftor therapy.

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.

Adherence to Nutritional Supplementation in Cystic Fibrosis.

PURPOSE: The purpose of this study was to examine patterns of adherence to a novel dietary supplement in pediatric cystic fibrosis. Adherence to dietary supplementation in cystic fibrosis is challenging, and examination of patterns of adherence behavior over time is needed to better characterize subgroups of patients who need self-management support. DESIGN AND METHODS: We prospectively examined adherence to Lym-X-Sorb™ (LXS), an organized lipid matrix dietary supplementation for patients with cystic fibrosis (CF) and pancreatic insufficiency (PI), over a 12-month period. Adherence for participants aged 5-17 years with CF and PI (N = 109) was monitored monthly via supplement packet counts. Group-based trajectory modeling was employed to examine patterns in adherence behavior over time. RESULTS: Four distinct trajectories best characterized adherence in this sample, with 18% of participants demonstrating near perfect adherence, 42% demonstrating good adherence (at or above 80%), 16% demonstrating poor adherence that declined over time, and 24% demonstrating significant non-adherence (< 30%). CONCLUSIONS: Some patients with CF and PI who are prescribed nutritional supplements will require intensive, individualized behavioral intervention to enhance adherence. Identifying patients who will have difficulty adhering to dietary interventions may result in better treatment-to-patient matching and improved adherence promotion efforts. PRACTICE IMPLICATIONS: Assessment of adherence to dietary supplementation over time can identify patients at risk for continued difficulty with self-management and provide opportunities for early intervention.

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.

Choline Supplementation With a Structured Lipid in Children With Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

BACKGROUND: Choline depletion is seen in cystic fibrosis (CF) and pancreatic insufficiency in spite of enzyme treatment and may result in liver, fatty acid, and muscle abnormalities. This study evaluated the efficacy and safety of an easily absorbed choline-rich structured lipid (LYM-X-SORB™ [LXS]) to improve choline status. METHODS: Children with CF and pancreatic insufficiency were randomized to LXS or placebo in a 12-month double blind trial. Dietary choline intake, plasma cholines, plasma and fecal phospholipids, coefficient of fat absorption, pulmonary function, growth status, body composition, and safety measures were assessed. Magnetic resonance spectroscopy for calf muscle choline and liver fat were assessed in a subgroup and compared with a healthy comparison group matched for age, sex, and body size. RESULTS: A total of 110 subjects were enrolled (age 10.4 ±â€Š3.0 years). Baseline dietary choline, 88% recommended, increased 3-fold in the LXS group. Plasma choline, betaine, and dimethylglycine increased in the LXS but not placebo (P = 0.007). Plasma lysophosphatidylcholine and phosphatidylcholine increased, and fecal phosphatidylcholine/phosphatidylethanolamine ratio decreased (P ≤ 0.05) in LXS only, accompanied by a 6% coefficient of fat absorption increase (P = 0.001). Children with CF had higher liver fat than healthy children and depleted calf muscle choline at baseline. Muscle choline concentration increased in LXS and was associated with improvement in plasma choline status. No relevant changes in safety measures were evident. CONCLUSIONS: LXS had improved choline intake, plasma choline status, and muscle choline stores compared with placebo group. The choline-rich supplement was safe, accepted by participants, and improved choline status in children with CF.

Effect of a dietary intervention on growth and energy expenditure in children with cystic fibrosis.

BACKGROUND: The study aim was to determine the effect of a dietary intervention on growth, body composition and resting energy expenditure (REE) in children with cystic fibrosis (CF) and pancreatic insufficiency (PI) in a randomized, double blind, placebo-controlled trial. METHODS: Subjects (5 to 17 yrs) participated in a 12-month trial of the organized lipid matrix LYM-X-SORB™ (LXS) vs. placebo dietary supplements with similar calories, total fat and fatty acids. Dietary intake was assessed using 3-day weighed food records. Height (HAZ), weight (WAZ), BMI (BMIZ), mid-upper arm muscle (UAMAZ) and fat area (UAFAZ) Z-scores were calculated. Fat mass (FM) and fat-free mass (FFM) were obtained by whole body DXA. REE (kcal/d) was evaluated by indirect calorimetry at baseline, 3 and 12 months and %REE calculated using Schofield equations. No growth or REE differences were observed between LXS and placebo groups so data were pooled for analysis. RESULTS: 63 children (57% males, age 10.6 ± 2.9 yr, 43% receiving LXS) completed REE measurements. Caloric intake increased from a median of 2502 [1478, 4909] to 2616 [1660, 4125] kcal/d at 12 months. HAZ, WAZ and UAMAZ increased (p < 0.05) over 12 months. Mean REE was 109 ± 8% predicted at baseline and 107 ± 9% at 12 months (p < 0.05). REE (kcal/d) adjusted for FFM and FM decreased over 12 months ([mean ± SE] -31 ± 12 kcals, p < 0.01), significant only in males (-49 ± 16 kcals, p < 0.01). CONCLUSIONS: Over a 12 month nutrition intervention with either LXS or placebo, the growth status, muscle stores and REE improved. Sustained increased energy intake improved energy metabolism, growth and nutritional status in school age children with CF, PI and mild lung disease.

Vitamin B(12) status in children with cystic fibrosis and pancreatic insufficiency.

OBJECTIVES: Unexpectedly high serum B12 concentrations were noted in most study subjects with cystic fibrosis (CF) and pancreatic insufficiency (PI) participating in a nutrition intervention at the baseline evaluation. The objectives of this study were to determine dietary, supplement-based, and enzyme-based B12 intake, serum B12 concentrations, and predictors of vitamin B12 status in children with CF and PI. STUDY DESIGN: Serum B12 status was assessed in subjects (5-18 years) and categorized as elevated (serum B12 above reference range for age and sex [Hi-B12]) or within reference range (serum B12 within reference range for age and sex) for age and sex. Serum homocysteine, plasma B6, red blood cell folate, height, weight, and body mass index z scores, pulmonary function, energy, and dietary and supplement-based vitamin intake were assessed. RESULTS: A total of 106 subjects, mean age 10.4 ±â€Š3.0 years, participated in the study. Median serum B12 was 1083 pg/mL, with 56% in the Hi-B12 group. Dietary and supplement-based B12 intakes were both high representing 376% and 667% recommended dietary allowance (RDA), respectively. The Hi-B12 group had significantly greater supplement-based B12 intake than the serum B12 within reference range for age and sex group (1000% vs 583% RDA, P < 0.001). Multiple logistic regression analysis showed that high supplement-based B12 intake and age >12 years increased the risk of Hi-B12, whereas higher forced expiratory volume at 1 second (FEV1) decreased the risk (pseudo-R = 0.18, P < 0.001). CONCLUSIONS: Serum B12 was elevated in the majority of children with CF and PI. Supplement-based B12 intake was 6 to 10 times the RDA, and strongly predicted elevated serum B12 status. The health consequences of lifelong high supplement-based B12 intake and high serum B12 are unknown and require further study, as does the inversed correlation between serum B12 and forced expiratory volume at 1 second.

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.

Update on fat-soluble vitamins in cystic fibrosis.

PURPOSE OF REVIEW: We review and critique recent scientific advances in the understanding of fat-soluble vitamins and the care of people with cystic fibrosis. RECENT FINDINGS: A shift in the conceptual approach to fat-soluble vitamin status has occurred. Vitamin status in cystic fibrosis had previously been discussed in terms of sufficiency versus insufficiency as compared with healthy populations. The discussion of vitamin status has now shifted to that of suboptimal versus optimal with respect to health outcomes. This is best illustrated by advances in the study of vitamin D. Newer metabolic and immunological roles and biomarkers have been identified. With supplementation of water-miscible formulations of preformed vitamin A, increased serum retinol has been observed, and may increase the risk for toxicity. SUMMARY: A paradigm shift has occurred in defining fat-soluble vitamin status by utilizing different biomarkers and associations with health outcomes. Identification of additional biomarkers, redefining definitions of adequacy, optimal surveillance for toxicity as well as adequacy is needed for care of patients with cystic fibrosis.

Vitamin A intake and elevated serum retinol levels in children and young adults with cystic fibrosis.

BACKGROUND: Individuals with cystic fibrosis (CF) and pancreatic insufficiency (PI) are at risk for fat-soluble vitamin deficiency, including vitamin A. Recent evidence suggests current practices of vitamin A intake results in elevated serum retinol. METHODS: Serum retinol was assessed in 78 subjects (8 to 25 years old) with CF and PI by high performance liquid chromatography, and compared to the U.S. National Health and Nutrition Examination Survey (NHANES) data of subjects of similar age and gender. Vitamin A intake, anthropometry and FEV(1) were measured, and their relationship to serum retinol status was assessed. RESULTS: Median (range) serum retinol was 80 microg/dL (33 to 208) in subjects with CF; 58% were above the NHANES reference range (30 to 72 microg/dL). Total vitamin A intake from diet and supplements was high (608+431% Recommended Dietary Allowance). Serum retinol was not correlated with vitamin A intake, age or gender, and was inversely correlated with weight and height z scores (r=-0.28, p<0.05) in the subjects with CF. CONCLUSIONS: Both vitamin A intake and serum retinol were elevated in subjects with CF and PI, corroborating recent evidence of elevated serum retinol in preadolescent children with CF. These findings indicate the need for further study of dosing and monitoring care practices of vitamin A, to ensure adequacy and to avoid toxicity.

Plasma zinc and growth status in preadolescent children with cystic fibrosis.

OBJECTIVE: To investigate plasma zinc status in relation to dietary and supplemental zinc intake, growth and pulmonary status in preadolescent children with cystic fibrosis (CF) and pancreatic insufficiency (PI). METHODS: Fasting plasma zinc was assessed in children (age, 8-11 years) with CF and PI. Food (7-day weighed records) and supplemental zinc intake, serum alkaline phosphatase and albumin, pulmonary function (spirometry), coefficient of fat absorption (%COA, 72-hour fecal fat) and growth status [height adjusted for genetic potential (AHAZ), weight (WAZ) and BMI Z scores (BMIZ)] were assessed. RESULTS: For the 62 children (32 males), mean plasma zinc (+/-SD) was 16.8 +/- 3.1 micromol/L (110 +/- 20 ug/dL). Sixty-five percent of the subjects had levels above the study reference range of 9.2 to 15.3 micromol/L (60-100 ug/dL); no subjects had low zinc levels. Median (range) total daily zinc intake was 279% (83-988%) recommended dietary allowance, growth status was suboptimal (mean +/- SD: AHAZ, -0.8 +/- 1.0; WAZ, -0.5 +/- 1.2; BMIZ, -0.2 +/- 1.1), and forced expiratory volume at 1 second (FEV1) was 92 +/- 13% predicted. Plasma zinc was not correlated with growth, pulmonary or alkaline phosphatase status. Plasma zinc was correlated with serum albumin (r = 0.25, P < 0.05) and was inversely correlated with coefficient of fat absorption (as %; r = -0.30, P = 0.02). CONCLUSIONS: Under current patterns of care in CF Centers, total zinc intake and plasma zinc status were adequate. These findings suggest that zinc was not a limiting micronutrient for preadolescent children with CF and PI and mild-to-moderate lung disease, and not likely contributing to their suboptimal growth status.