Effect of docosahexaenoic acid on lipoprotein subclasses in hyperlipidemic children (the EARLY study)

doi:10.1016/j.amjcard.2004.12.014

The American Journal of Cardiology

Volume 95, Issue 7, 1 April 2005, Pages 869-871

https://doi.org/10.1016/j.amjcard.2004.12.014 Get rights and content

To test the hypothesis that a dietary ω-3 fatty acid, docosahexaenoic acid, improves the lipoprotein subclass profile of children who have hyperlipidemia, we conducted a randomized, double-blind, placebo-controlled study. Children who had hyperlipidemia (n = 20) were stabilized on a low-fat diet for 6 weeks and then randomized to receive 1.2 g/day of docosahexaenoic acid for 6 weeks or placebo. Supplementation with docosahexaenoic acid significantly increased low-density lipoprotein subclass 1 and high-density lipoprotein subclass 2 (large and buoyant; less atherogenic particles) by 91% and 14%, respectively, compared with the placebo phase. Low-density lipoprotein subclass 3 (small and dense; more atherogenic particles) decreased by 48%.

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Acknowledgment

We sincerely appreciate the exceptional expertise and assistance provided by the nurses and laboratory staff in the Pediatric Clinical Research Center and the dietetic staff of the General Clinical Research Center at the University of California–San Francisco Medical Center, San Francisco, California. We also thank Martek Biosciences Corporation (Columbia, Maryland) for kindly providing the supplements.

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Fish oil improves cardiometabolic markers in adults, but results in children are inconsistent. Few children meet the recommended fish intake and no randomized trials have investigated how fish intake per se affects children–s cardiometabolic profile.
We investigated whether oily fish consumption modulated serum triacylglycerol and diastolic blood pressure (coprimary outcomes) and other cardiometabolic markers in healthy Danish children and whether effects were sex-specific.
In a randomized controlled 12-wk trial, 199 children (aged 8–9 y) received ∼300 g/wk of oily fish or poultry (control). We measured blood pressure, heart rate, and heart rate variability (HRV) via 3-h continuous electrocardiograms and collected fasting blood samples for analysis of erythrocyte EPA [20:5n–3 (ω-3)] + DHA (22:6n–3) and serum triacylglycerol, LDL and HDL cholesterol, glucose, and insulin.
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Oily fish intake improved serum triacylglycerol and HDL cholesterol in a dose-dependent manner in 8- to 9-y-old children, but had no effect on blood pressure, HRV, or glucose homeostasis. This supports recommendations for fish intake in children and underlines the importance of initiatives to increase children–s intake of oily fish. This trial was registered at clinicaltrials.gov as NCT02809508.
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Central obesity, dyslipidaemia, hyperglycaemia, and hypertension are typical features of metabolic syndrome that seem to hesitate often in type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and many other clinical conditions. Thus preventing and curing metabolic syndrome in paediatric patients is becoming an urgent need for public health.
While diagnostic criteria and therapy of metabolic syndrome in adults are very well defined, there is no consensus on the definition of metabolic syndrome in children and adolescents as well as on healing approaches.
The aim of this review is to describe the recent advances on the pathogenesis and clinical outcomes of paediatric metabolic syndrome. We then detail the therapeutic strategies (i.e. dietary regimens, physical exercise, nutraceuticals, and medications) employed to manage the disease. Finally, we analyse the safety profile of the drugs used in children and adolescents by performing a retrospective review of paediatric adverse reactions reported in the FDA’s Adverse Event Reporting System database.
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Familial hypercholesterolemia (FH) is a common genetic disorder that causes elevated LDL cholesterol levels from birth. Untreated FH accelerates atherosclerosis and predisposes individuals to premature coronary artery disease (CAD) in adulthood. Mendelian randomization studies have demonstrated that LDL cholesterol has both a causal and cumulative effect on the risk of CAD. This supports clinical recommendations that children with FH commence pharmacological treatment from the age of 8 to 10 years, to reduce the burden of hypercholesterolemia. Worldwide, the majority of children with FH remain undiagnosed. Recent evidence suggests that the frequency of FH is at least 1 in 250 and this constitutes a public health issue. We review and identify the knowns and unknowns concerning the detection and management of pediatric FH that impact on the developing model of care for this condition.
A double-blind randomized trial of fish oil to lower triglycerides and improve cardiometabolic risk in adolescents
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There are limited clinical trial data on the use of fish oil for cardiovascular risk reduction in childhood. Engler et al13 showed in children with dyslipidemia that 1.2 g/day of DHA increased concentrations of larger LDL and HDL particles and decreased concentrations of smaller LDL particles. Pedersen et al14 compared fish oil with vegetable oil contained in bread at a 1.5 g/day dose in 78 mildly overweight Danish boys.
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Participants (n = 42, age 14 ± 2 years) with hypertriglyceridemia and low-density lipoprotein (LDL) cholesterol <160 mg/dL were enrolled in a randomized, double-blind, crossover trial comparing 4 g of fish oil daily with placebo. Treatment interval was 8 weeks with a 4-week washout. Lipid profile, lipoprotein particle distribution and size, glucose, insulin, high-sensitivity C-reactive protein, interleukin-6, fibrinogen, plasminogen activator inhibitor-1, and thrombin generation were measured.
Baseline lipid profile was total cholesterol 194 (5.4) mg/dL (mean [SE]), triglycerides 272 (21) mg/dL, high-density lipoprotein cholesterol 39 (1) mg/dL, and LDL cholesterol 112 (3.7) mg/dl. LDL particle number was 1614 (60) nmol/L, LDL size was 19.9 (1.4) nm, and large very low-density lipoprotein/chylomicron particle number was 9.6 (1.4) nmol/L. Triglycerides decreased on fish oil treatment but the difference was not significant compared with placebo (−52 ± 16 mg/dL vs −16 ± 16 mg/dL). Large very low-density lipoprotein particle number was reduced (−5.83 ± 1.29 nmol/L vs −0.96 ± 1.31 nmol/L; P < .0001). There was no change in LDL particle number or size. There was a trend towards a lower prothrombotic state (lower fibrinogen and plasminogen activator inhibitor-1; .10 > P > .05); no other group differences were seen.
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: This research was supported by Grant NR 04902 from the National Institutes of Health, Bethesda, Maryland. Studies performed in the Pediatric Clinical Research Center and the General Clinical Research Center, University of California at San Francisco were funded by Grants MOI RR-01271 and MOI-00079, respectively, from the National Center for Research Resources, United States Public Health Service, Washington, DC.

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Brief reportsEffect of docosahexaenoic acid on lipoprotein subclasses in hyperlipidemic children (the EARLY study)

Section snippets

Acknowledgment

Eur J Pharmacol

Nutr Res

Am J Clin Nutr

J Lipid Res

Atherosclerosis

Atherosclerosis

Am J Clin Nutr

Atherosclerosis

Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association

Arterioscler Thromb Vasc Biol

Effects of docosahexaenoic acid on vascular pathology and reactivity in hypertension

Exp Biol Med

Brief reports
Effect of docosahexaenoic acid on lipoprotein subclasses in hyperlipidemic children (the EARLY study)