A randomized placebo-controlled study on high-dose oral algal docosahexaenoic acid supplementation in children with cystic fibrosis

Alicandro, Gianfranco; Faelli, Nadia; Gagliardini, R.; Santini, B; Magazzù, Giuseppe; Biffi, A.; Risé, Patrizia; Galli, C.; Tirelli, Amedea Silvia; Loi, Sherene; Valmarana, L.; Cirilli, N.; Palmas, T.; Vieni, Giuseppe; Bianchi, Maria Luisa; Agostoni, Carlo; Colombo, Claudio

doi:10.1016/j.plefa.2012.10.002

Cited by 31 publications

(38 citation statements)

References 36 publications

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“…LA levels were higher than previously reported for pediatric CF patients (21–23). This could explain why an increase in LA levels was not seen with DHA supplementation.…”

Section: Discussioncontrasting

confidence: 78%

Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study

O'Connor

Thomsen

Brown

et al. 2016

Prostaglandins, Leukotrienes and Essential Fatty Acids

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Background Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). Methods This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6 to 18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Results Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Conclusions Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation.

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“…LA levels were higher than previously reported for pediatric CF patients (21–23). This could explain why an increase in LA levels was not seen with DHA supplementation.…”

Section: Discussioncontrasting

confidence: 78%

Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study

O'Connor

Thomsen

Brown

et al. 2016

Prostaglandins, Leukotrienes and Essential Fatty Acids

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“…However, data on clinical improvements by docosahexaenoic acid (C22:6) are conflicting [22,28,29,30]. LC-PUFA metabolism is intimately linked to that of choline, since PC is a major LC-PUFA carrier between the liver and other organs.…”

Section: Discussionmentioning

confidence: 99%

“…In this context C20:4 and C22:6 status and supplementation have been investigated extensively in CF. Whereas C22:6 supplementation in neutral lipid form did not convincingly improve clinical outcome [29,30], there is so far no focus on choline deficiency, impaired PC homeostasis, and their link to C20:4 and C22:6 metabolism, in relation to clinical parameters. The data of this study, however, indicate that in CF decreased plasma choline and total PC, and their link to LC-PUFA via C20:4-PC and C22:6-PC metabolism, specifically relates to lung function impairment and inflammation.…”

Section: Discussionmentioning

confidence: 99%

Plasma Phosphatidylcholine Alterations in Cystic Fibrosis Patients: Impaired Metabolism and Correlation with Lung Function and Inflammation

Grothe

Riethmüller²,

Tschürtz³

et al. 2015

Cell Physiol Biochem

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Background: Liver impairment, ranging from steatosis to cirrhosis, is frequent in cystic fibrosis (CF) patients and is becoming increasingly significant due to their improved life expectancy. One aspect of hepatic alterations is caused by increased fecal loss of the essential nutrient choline, following enterohepatic bile phosphatidylcholine (PC) cycle impairment. Hepatic PC synthesis, both de novo and via phosphatidylethanolamine-N-methyl-transferase (PEMT), is essential for very low-density lipoprotein (VLDL) secretion. VLDL-PC in particular contributes to the organism's supply with polyunsaturated fatty acids (LC-PUFA), namely arachidonic (C20:4) and docosahexaenoic acid (C22:6). Consequently, choline deprivation and altered hepatic PC metabolism may affect plasma PC homeostasis and extrahepatic organ function. Objectives: To investigate relationships between altered plasma choline and PC homeostasis and markers of lung function and inflammation in CF. To assess alterations in hepatic choline and PC metabolism of CF patients. Design: Quantification of plasma/serum choline and PC species in adult CF patients compared to controls. Correlation of PC with forced expiratory vital capacity (FEV₁) and interleukin 6 (IL-6) concentrations. Analysis of choline and PC metabolism in CF compared to controls, using deuterated choline ([D₉-methyl]-choline) labeling in vivo. Results: Mean choline and PC concentrations in CF patients were lower than in controls. Choline and PC concentrations as well as fractions of C22:6-PC and C20:4-PC correlated directly with FEV₁, but inversely with IL-6. Plasma concentrations of deuterated PC were decreased for both pathways, whereas only in PC synthesized via PEMT precursor enrichment was decreased. Conclusion: In CF patients, hepatic and plasma homeostasis of choline and PC correlate with lung function and inflammation. Impaired hepatic PC metabolism, exemplarily shown in three CF patients, provides an explanation for such correlations. Larger studies are required to understand the link between hepatic PC metabolism and overall clinical performance of CF patients, and the perspective of choline substitution of these patients.

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“…Serum concentrations of retinol and a-tocopherol (another lipidsoluble vitamin) were measured by HPLC (Waters) according to the manufacturerÕs instructions (Chromsystems Diagnostics) (12). Serum RBP4 concentrations were measured in serum samples by ELISA according to the manufacturerÕs instructions (Abcam) (5).…”

Section: Study Cohortsmentioning

confidence: 99%

PNPLA3 I148M Variant Influences Circulating Retinol in Adults with Nonalcoholic Fatty Liver Disease or Obesity ,

Mondul

Mancina

Merlo

et al. 2015

The Journal of Nutrition

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A randomized placebo-controlled study on high-dose oral algal docosahexaenoic acid supplementation in children with cystic fibrosis

Cited by 31 publications

References 36 publications

Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study

Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study

Plasma Phosphatidylcholine Alterations in Cystic Fibrosis Patients: Impaired Metabolism and Correlation with Lung Function and Inflammation

PNPLA3 I148M Variant Influences Circulating Retinol in Adults with Nonalcoholic Fatty Liver Disease or Obesity ,

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