Oral DHA supplementation in ΔF508 homozygous cystic fibrosis patients

Biervliet, S. Van; Devos, Michaël; Delhaye, T.; Biervliet, J.P. Van; Robberecht, Eddy; Christophe, Armand

doi:10.1016/j.plefa.2007.12.005

Cited by 54 publications

(41 citation statements)

References 37 publications

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“…Explanation for the low levels of DHA present throughout the study is less evident if we take into account that plasma levels of this fatty acid are not exclusively dependent on exocrine pancreatic function (24). Competitive metabolism with fatty acids 6 or accentuated catabolism could be in cause (25).…”

Section: Discussionmentioning

confidence: 97%

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Persistence of Essential Fatty Acid Deficiency in Cystic Fibrosis Despite Nutritional Therapy

et al. 2009

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ABSTRACT:To study the evolution of plasma fatty acid composition of patients with cystic fibrosis (CF) in relation to nutritional status, pancreatic function, and development of CF-related liver disease (CFRLD) and diabetes mellitus, 24 CF pediatric patients with stable pulmonary disease were studied before and after an approximate period of 8 y. Nutritional status, pulmonary function, pancreatic function, and presence of CFRLD or diabetes mellitus were recorded. Results were compared with data obtained in 83 healthy children. Patients with CF have significantly lower linoleic acid (LA), docosahexaenoic acid (DHA), lignoceric acid, and LA ϫ DHA product and higher oleic acid, mead acid, dihomo-␥-linoleic acid, and docosapentaenoic acid (DPA). Comparison of samples taken at first and second studies revealed a significant decrease in LA levels and lignoceric acid associated with a significant increase in dihomo-␥-linoleic acid levels. Patients with CFRLD showed significantly higher mead acid/arachidonic acid ratio and lower total 6 polyunsaturated fatty acids content. There was no relation of plasma fatty acids composition with pancreatic function, pulmonary function, or diabetes mellitus. Follow-up of patients with CF shows that essential fatty acids deficiency, particularly in LA and DHA content, persisted unmodified along time despite an adequate nutritional therapy. Future studies after supplementation with 3 polyunsaturated fatty acids should be undertaken. (Pediatr Res 66: 585-589, 2009)

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Section: Discussionmentioning

confidence: 97%

“…These mediators are involved in the resolution phase of the inflammatory process, which, as mentioned, is enhanced in patients with CF. A decreased bioavailability of DHA may, therefore, have a deleterious effect on tissue functionality and, particularly, on pulmonary and pancreatic cells (24).…”

Section: Discussionmentioning

confidence: 99%

Persistence of Essential Fatty Acid Deficiency in Cystic Fibrosis Despite Nutritional Therapy

et al. 2009

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“…Investigators have shown that oral administration of DHA to cftr 2/2 mice corrected the lipid imbalance and reversed the observed pathological manifestations (Freedman et al 2002;Beharry et al 2007). There have been a handful of studies of DHA supplementation in CF patients (Van Biervliet et al 2008;Aldamiz-Echevarria et al 2009). Unfortunately, the dose of DHA, study size, duration of treatment, and outcome measures vary widely.…”

Section: Eicosanoid Modulatorsmentioning

confidence: 99%

Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

Chmiel

Konstan

Elborn

2013

Cold Spring Harbor Perspectives in Medicine

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“…Furthermore, this treatment corrected the phenotypic manifestations of CF, decreasing ileal villus height, pancreatic duct diameter, and pulmonary infl ammation stimulated by lipopolysaccharide ( 6,25 ). Similarly, CF patients treated with DHA exhibited signifi cant decreases in plasma AA levels (26)(27)(28), accompanied in some cases by increased LA ( 29,30 ). Despite moving the fatty acid alterations in CF toward normal, the clinical outcomes in these small studies have been inconsistent.…”

Section: Fatty Acid Labeling Experimentsmentioning

confidence: 99%

DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity

Njoroge

Laposata²,

Katrangi³

et al. 2012

Journal of Lipid Research

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in the United States to 37 years ( 2 ). Among the phenotypic manifestations of CF patients are abnormalities in blood and tissue polyunsaturated fatty acid (PUFA) levels that are independent of absorption and nutritional status (reviewed in Refs. [3][4][5]. The most consistent of these abnormalities are decreased linoleate (LA; 18:2n-6) and docosahexaenate (DHA; 22:6n-3). In addition, some studies have shown increased arachidonate (AA; 20:4n-6), palmitoleate (16:1n-7), oleate (18:1n-9), and Mead acid (20:3n-9). Similar fi ndings are seen in animal ( 6-9 ) and cell culture ( 10, 11 ) models of CF. The magnitude of fatty acid alterations in CF patients correlates with disease severity, suggesting a role for fatty acid metabolism in CF pathophysiology ( 12-17 ).There is increasing evidence that these abnormalities are due to differences in fatty acid metabolism in CF. PUFAs of the n-3 and n-6 series are metabolized in a stepwise fashion along parallel pathways (reviewed in Ref. 18 ). A common set of desaturase and elongase enzymes catalyzes the conversion of LA through multiple steps to AA and ultimately to docosapentaenoate (DPA; 22:5n-6). The same enzymes convert linolenate (LNA; 18:3n-3) to eicosapentaenoate (EPA; 20:5n-3) and subsequently to DHA. Multiple studies have demonstrated increased conversion of AA to eicosanoids (19)(20)(21)(22), stimulating increased metabolism of LA to maintain AA ( 7, 10, 11 ) and accounting for the decreased LA and increased AA levels seen in CF.Recent studies in our laboratory have uncovered a potential mechanism accounting for these metabolic changes ( 23 ). In cell culture models of CF, decreased LA and increased AA and EPA levels in CF cells correlated with increased expression and activity of the ⌬ 5-and ⌬ 6-desaturase enzymes that catalyze conversion of LA to AA and LNA to EPA. Similar increases in ⌬ 9-desaturase and elongase-6Abstract Patients and models of cystic fi brosis (CF) exhibit consistent abnormalities of polyunsaturated fatty acid composition, including decreased linoleate (LA) and docosahexaenoate (DHA) and variably increased arachidonate (AA), related in part to increased expression and activity of fatty acid desaturases. These abnormalities and the consequent CF-related pathologic manifestations can be reversed in CF mouse models by dietary supplementation with DHA. However, the mechanism is unknown. This study investigates this mechanism by measuring the effect of exogenous DHA and eicosapentaenoate (EPA) supplementation on fatty acid composition and metabolism, as well as on metabolic enzyme expression, in a cell culture model of CF. We found that both DHA and EPA suppress the expression and activity of ⌬ 5-and ⌬ 6-desaturases, leading to decreased fl ux through the n-3 and n-6 PUFA metabolic pathways and decreased production of AA. The fi ndings also uncover other metabolic abnormalities, including increased fatty acid uptake and markedly increased retroconversion of DHA to EPA, in CF cells. These results indicate that the fatty acid abnormalities of CF are ...

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Oral DHA supplementation in ΔF508 homozygous cystic fibrosis patients

Cited by 54 publications

References 37 publications

Persistence of Essential Fatty Acid Deficiency in Cystic Fibrosis Despite Nutritional Therapy

Persistence of Essential Fatty Acid Deficiency in Cystic Fibrosis Despite Nutritional Therapy

Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity

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