Dietary supplementation with docosahexanoic acid (DHA) increases red blood cell membrane flexibility in mice with sickle cell disease

Wandersee, Nancy J.; Maciaszek, Jamie L.; Giger, Katie; Hanson, Madelyn S.; Zheng, Shan Suo; Guo, Yihe; Mickelson, Barbara; Hillery, Cheryl A.; Lykotrafitis, George; Low, Philip S.; Hogg, Neil

doi:10.1016/j.bcmd.2014.11.004

Cited by 25 publications

(14 citation statements)

References 67 publications

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“…These findings indicated the important role of fatty acid abnormality in the chronic inflammatory state associated with the disease [14,15]. In addition, our group and others have shown that supplementing SCD patients with omega-3 fatty acids corrects cell membrane abnormalities and confer protection against vaso-occlusive pain episodes, severe anaemia and oxidative stress [16][17][18][19], and improves red blood cells flexibility in mice [20]. However, little is known about the potential antiinflammatory role of n−3 fatty acids in SCD.…”

Section: Introductionmentioning

confidence: 53%

Omega 3 (n−3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease

Daak

Elderdery

Elbashir

et al. 2015

Blood Cells, Molecules, and Diseases

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Chronic inflammation and reduced blood levels of omega-3 fatty acids (n−3) are known characteristics of sickle cell disease (SCD).The anti-inflammatory properties of n−3 fatty acids are well recognized. Omega-3 treated (n = 24), hydroxyurea (HU) treated (n = 18), and n−3 untreated (n = 21) homozygous SCD patients (HbSS) and healthy (HbAA) controls (n = 25) matched for age (5-16 years), gender and socioeconomic status were studied. According to age (5-10) or (11-16) years, two or three capsules containing 277.8 mg docosahexaenoic (DHA) and 39.0 mg eicosapentaenoic (EPA) or high oleic acid placebo (41%) were assigned to n − 3 treated and n − 3 untreated groups, respectively. Hydroxyurea treated group was on dosage more than 20 mg/kg/day. The effect of supplementation on systemic and blood cell markers of inflammation was investigated. The n− 3 treated group had higher levels of DHA and EPA (p b 0.001) and lower white blood cell count and monocyte integrin (p b 0.05) compared with the n−3 untreated. No difference was detected between the two groups regarding C-reactive protein, granulocytes integrin and selectin, plasma tumour necrosis factor-α and interleukin-10. The n−3 treated group had lowered nuclear factor-kappa B (NF-κB) gene expression compared to n−3 untreated and HU treated groups (p b 0.05). This study provides evidence that supplementation with n− 3 fatty acids may ameliorate inflammation and blood cell adhesion in patients with SCD.

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Section: Introductionmentioning

confidence: 53%

Omega 3 (n−3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease

Daak

Elderdery

Elbashir

et al. 2015

Blood Cells, Molecules, and Diseases

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“…Interestingly, v-3 fatty acids are considered to be a multitarget intervention; in addition to having an antioxidative effect, they have been shown to inhibit platelet activation and blood-cell aggregation and inflammation and improve cell-membrane deformability. 65,[79][80][81][82] However, further confirmation of its efficacy on clinical outcomes is needed. The fact that 2 new phase 3 multicenter studies are expected to start enrollment soon therefore offers hope (registered at www.clinicaltrials.gov as #NCT02604368 and #NCT02525107).…”

Section: Discussionmentioning

confidence: 99%

Pharmacotherapeutical strategies in the prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review

et al. 2017

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Sickle-cell disease (SCD) is characterized by frequent and painful vaso-occlusive crises (VOCs).Various treatments have been evaluated over the years. However, a clear overview is lacking.The objective of this study was to systematically review all pharmacotherapeutical strategies in the prevention of VOCs beyond hydroxyurea. We performed a systematic literature search (MEDLINE, Embase, CENTRAL). Eligible studies were controlled clinical trials evaluating pharmacotherapeutical interventions targeting the reduction of VOCs in patients with SCD.Primary outcomes were the number or duration of SCD-related pain days, VOCs, or hospital admissions for VOCs. Secondary outcomes included time to first VOC or hospital admission for a VOC. A standardized data extraction sheet was used. The methodological quality of studies was assessed using Cochrane's risk-of-bias tool. A total of 36 studies were included in this review, covering 26 different prophylactic interventions. The most promising interventions for reducing the frequency of either VOCs or hospitalizations were the oral antioxidants L-glutamine and v-3 fatty acids and the IV antiadhesive agent crizanlizumab. Twenty-three studies did not show any beneficial effect of the intervention under investigation, and 6 studies were either too small or methodologically inadequate to draw conclusions. Because of the heterogeneity of interventions, no meta-analysis was performed. In conclusion, this review identified 3 promising pharmacotherapeutical strategies in the prevention of VOCs in SCD. Importantly, this study highlights the discrepancy between the significant burden of SCD worldwide and the low number of adequate trials performed. This review was

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“…In a recent important study, Wandersee et al 93 is trying to investigate the therapeutic potential of ω-3 fatty acids for patients with homozygous sickle cell disease in a randomised, placebo-controlled, double-blind trial. Preliminary results indicate that supplementation with ω-3 fatty acids may improve inflammation and blood cell adhesion in patients with SCD.…”

Section: ω-3 Treatmentmentioning

confidence: 99%

Insight into the complex pathophysiology of sickle cell anaemia and possible treatment

Piccin

Murphy

Eakins

et al. 2019

European J of Haematology

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Sickle cell anaemia (SCA) is the consequence of abnormal haemoglobin production due to an inherited point mutation in the β‐globin gene. The resulting haemoglobin tetramer is poorly soluble when deoxygenated, and when this is prolonged, intracellular gelation of sickle haemoglobin occurs, followed by haemoglobin polymerisation. If many cycles of sickling and unsickling occur, the red cell membrane will be disrupted leading to haemolysis and vaso‐occlusive events. Recent studies have also shown that leucocyte adhesion molecules and nitric oxide (NO) depletion are involved in endothelial damage. New insights in SCA pathophysiology and vascular biology have shown that cell‐derived microparticle (MP) generation is also involved in the vaso‐occlusion. Endothelial damage is perpetuated by impaired production or increased consumption of protective modulators such as protein C, protein S and NO. New therapeutic interventions should address these aspects of SCA pathogenesis. To date, the only US‐FDA‐approved therapy to prevent painful vaso‐occulsive episodes is hydroxyurea that reduces haemoglobin polymerisation in sickle cells by increasing the production of foetal haemoglobin and L‐glutamine. However, several new drugs have been tested in the last years in randomised clinical trials. We here report an update on the current status of knowledge on SCA.

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Dietary supplementation with docosahexanoic acid (DHA) increases red blood cell membrane flexibility in mice with sickle cell disease

Cited by 25 publications

References 67 publications

Omega 3 (n−3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease

Omega 3 (n−3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease

Pharmacotherapeutical strategies in the prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review

Insight into the complex pathophysiology of sickle cell anaemia and possible treatment

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