Clinical Pediatrics

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Effectiveness of Omega-3 Polysaturated Fatty Acids (Fish Oil) Supplementation for Treating
Hypertriglyceridemia in Children and Adolescents
Nita Chahal, Cedric Manlhiot, Helen Wong and Brian W. McCrindle
CLIN PEDIATR 2014 53: 645 originally published online 18 March 2014
DOI: 10.1177/0009922814527503

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research-article2014
CPJXXX10.1177/0009922814527503Chahal et alClinical PediatricsChahal et al

Article
Clinical Pediatrics

Effectiveness of Omega-3 Polysaturated 2014, Vol. 53(7) 645­–651

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DOI: 10.1177/0009922814527503

for Treating Hypertriglyceridemia in cpj.sagepub.com

Children and Adolescents

Nita Chahal, RN(EC), MN, NP Peds1, Cedric Manlhiot, BSc1,

Helen Wong, RD1, and Brian W. McCrindle, MD, MPH1

Abstract
Limited pharmacological options are available for management pediatric hypertriglyceridemia. We examined the
effectiveness of dietary fish oil supplementation as a means to reduce triglyceride levels in pediatric patients. We
reviewed 111 children aged 8 to 18 years with hypertriglyceridemia (≥1.5 mmol/L) undergoing treatment in a
specialized dyslipidemia clinic. At the treating cardiologist’s discretion, 60 subjects received nonprescription fish oil
supplementation (500-1000 mg/d), while the remaining patients did not. Initially there were no baseline differences
between groups, including the use of concomitant lipid-lowering medication. Treatment with fish oil was associated
with a potential clinically relevant but non-statistically significant decrease in triglycerides and triglyceride-to-
high-density lipoprotein (HDL) ratio. Fish oil had no effect on HDL-cholesterol, non-HDL-cholesterol, or total
cholesterol. All associations remained unchanged when adjusted for body mass index z score, nutrition, physical
activity, and screen time. Fish oil supplementation was not significantly effective in treating hypertriglyceridemia in
pediatric patients.

Keywords
dyslipidemia, pediatrics, fish oil, treatment

Introduction Recent investigations in adults suggest that

Pediatric hypertriglyceridemia is multifactorial in
nature, with both genetic and lifestyle-related factors
contributing to elevated triglyceride (TG) levels.1 The
incidence is rising because of the ongoing pediatric
obesity epidemic. Current evidence suggests that ele-
vated TG levels likely contribute independently to an
increased risk of cardiovascular disease (CVD), albeit
to a lesser degree than elevated low-density lipoprotein
cholesterol (LDL-C) levels.2-8 The lipid profile of pedi-
atric patients with hypertriglyceridemia usually
includes decreased high-density lipoprotein choles-
terol (HDL-C) levels, and may include elevations in
non-HDL-cholesterol. In the context of obesity, HDL-C
and LDL-C also undergo qualitative changes, includ-
ing reduced volume and increased density, resulting in
potentially dysfunctional HDL and LDL particles,
which are more susceptible to changes in clearance,
oxidative modifications, and overall increased athero-
genicity.9 This association is magnified in the presence
of hypertriglyceridemia.10
TG-lowering medications (fibrates, nicotinic acid, or
fish oil) aimed at reducing TG levels probably results in
a net benefit and may be complementary to a strategy
aimed at reducing LDL-C levels.11,12 In pediatric
patients, lipid-lowering medication is reserved only for
the most severe cases, as long-term safety and efficacy
remains to be established.13 As such, lifestyle modifica-
tions remain the cornerstone for management of pediat-
ric dyslipidemias. The use of lipid-lowering dietary
supplements in this context is a potential avenue to pro-
vide risk reduction without drug exposure.14,15 In this
retrospective review, we sought to determine the effect
of fish oil (omega-3) supplementation on the lipid
1
Labatt Family Heart Centre, The Hospital for Sick Children,
Toronto, Ontario, Canada
Corresponding Author:
Brian W. McCrindle, Labatt Family Heart Centre, The Hospital for
Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8,
Canada.
Email: brian.mccrindle@sickkids.ca

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646 Clinical Pediatrics 53(7)
profile of children with hypertriglyceridemia managed
primarily through healthy lifestyle behavior change in a
specialized pediatric lipid disorders clinic.
Methods
All patients assessed at the Hospital for Sick Children
Pediatric Lipid Disorder Clinic (Toronto, Ontario,
Canada) after 1995 for hypertriglyceridemia (defined as
at least one TG level ≥1.5 mmol/L1) were eligible for
inclusion in this review. Patients with homozygous
familial hypercholesterolemia were excluded. All fol-
low-up visit information up to December 2010 was
included in the current analysis. Patients followed in the
clinic were usually assessed every 3 to 6 months depend-
ing on the severity of each patient’s lipid profile. The
study was approved by the institutional research ethics
board; requirement for individual patient consent was
waived for this retrospective study.
First clinical assessment and laboratory information
were considered as baseline and, thereafter, all subse-
quent visit data were reviewed and included in analysis.
The American Heart Association recommends dietary
supplementation with 1000 mg of fish or fish oil daily
for adult patients under physician observation who have
clinical history of cardiovascular disease, or a 2000- to
4000-mg supplement for the management of those with
elevated TGs.16 There are no specific fish oil dosage rec-
ommendations for the pediatric population. Our clinical
use of fish oil supplementation was based on modifica-
tion of the American Heart Association recommenda-
tions for adults. The children with elevated TGs (≥1.5
mmol/L) were recommended to start 500 mg (<10 years
old) or 1000 mg (≥10 years old) of fish oil supplementa-
tion (nonprescription, over the counter) per day. Before
starting supplementation, it was confirmed with the
patient and family that there was no allergy to fish or
fish products. Compliance was assessed by self- report
at follow-up visits. Patients were also directed to stop
taking fish oil supplementation if they developed a skin
rash, itching, swelling, difficulty in breathing and to
immediately seek emergency medical help.
Data were obtained from either the patient’s medical
record or computerized lipid clinic database. Relevant
medication use (statins and fish oil), height, weight,
waist measurement, blood pressure, and fasting lipid
values were abstracted for each clinic visit. Medications
that were used infrequently, for example, bile acid
sequestrant (n = 1), fenofibrates (n = 2), and ezetimibe
(n = 1), could not be considered in the analysis. Family
history was reviewed for all patients and was considered
positive if family members had known hyperlipidemia
or a history of premature CVD.
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Figure 1.  Ten-point scale to assess patient’s compliance
with low-fat prudent diet.
Age- and gender-based body mass index (BMI) z
score was calculated using the algorithm provided by
the Division of Nutrition and Physical Activity of the
Centers for Disease Control and Prevention, Atlanta,
Georgia.17 In recent years, waist circumference and
waist-to-height ratio were incorporated into routine
patient assessment.18 Physical activity and screen time
(reported as hours per week) were calculated from pre-
viously validated questionnaires19 completed by the
patients in the week prior to clinical assessment. Patient
compliance with a low-fat prudent diet (prescribed as
part of patient treatment for hypertriglyceridemia) was
rated on a 10-point scale (derived from published guide-
lines20-22) based on the assessment of the clinical dieti-
tian using a predetermined scale (Figure 1). A total
dietary score of 1 to 3 out of 10 indicates a poor score, 4
to 5 indicates a fair score, 6 to 7 indicates a good score,
8 to 9 indicates a very good score, and 10 out of 10 indi-
cates an excellent score. Data are described as frequen-
cies, medians with interquartile range, and means with
standard deviation as appropriate. In a first time we
compared the overall characteristics (those not changing
over time) and medical status of referral of patients who
ever received fish oil to those who did not using
Student’s t tests (unequal variance between samples)
and Fisher’s exact χ2. Lipid profiles over time were
modeled in linear regression models adjusted for
repeated measures with a compound symmetry covari-
ance structure. Effect of fish oil and statin treatment on
lipid profiles was evaluated in those regression models.
These models were all repeated, including BMI z score,
nutrition score, physical activity, and screen time as
Chahal et al 647

Table 1.  Patient Characteristics at Baseline.

N No Fish Oil (n = 51) N Fish Oil (n = 60) P

Age in years at referral, mean ± SD 51 10.5 ± 3.6 60 11.0 ± 3.6 .44
Male gender, n (%) 51 25 (49) 60 36 (60) .26
Duration in years of follow-up, median (IQR) 51 2.5 (1.1 to 5.2) 60 1.7 (1.0 to 3.4) .10
Total number of visits, median (IQR) 51 5 (3 to 8) 60 4 (3 to 7) .85
Diabetes mellitus, n (%) 51 4 (8) 60 0 (0) .04
Affected sibling(s), n (%) 36 10 (28) 34 8 (24) .79
Affected parent(s), n (%) 41 31 (76) 52 41 (79) .80
Affected grandparent(s), n (%) 37 33 (89) 44 35 (80) .36
Behavior  
  Nutrition score, mean ± SD 16 5.2 ± 2.1 36 5.1 ± 2.2 .87
  Weekly physical activity (hours), mean ± SD 22 3.5 ± 2.6 34 4.4 ± 2.9 .19
  Weekly screen time (hours), mean ± SD 25 5.1 ± 2.2 35 22.3 ± 14.2 .55
Medical status at referral  
  BMI in kg/m2, mean ± SD 50 23.9 ± 6.0 56 24.2 ± 6.4 .81
 BMI z score, median (IQR) 47 +2.1 (+1.0 to +3.0) 52 +2.0 (+1.2 to +2.8) .91
  Waist in cm, mean ± SD 12 90 ± 13 24 83 ± 15 .14
  Waist-to-height ratio, mean ± SD 12 0.59 ± 0.07 24 0.55 ± 0.08 .10
  Systolic blood pressure in mm Hg, mean ± SD 43 114 ± 15 52 113 ± 12 .69
  Systolic blood pressure z score, median (IQR) 41 +0.9 (−0.1 to +1.8) 50 +0.4 (+0.1 to +1.1) .20
  Diastolic blood pressure in mm Hg, mean ± SD 43 66 ± 7 52 67 ± 8 .56
  Diastolic blood pressure z score, median (IQR) 41 +0.2 (−0.1 to +1.0) 50 +0.3 (−0.1 to +0.9) .82
  Pulse pressure in mm Hg, mean ± SD 29 81 ± 13 39 84 ± 18 .50
  Fasting total cholesterol in mmol/L, mean ± SD 51 5.58 ± 1.27 58 5.50 ± 1.36 .75
  Fasting LDL-cholesterol in mmol/L, mean ± SD 47 3.63 ± 1.42 47 3.54 ± 1.32 .75
  Fasting HDL-cholesterol in mmol/L, mean ± SD 51 1.05 ± 0.31 57 0.95 ± 0.31 .11
  Fasting non-HDL-cholesterol in mmol/L, mean ± SD 51 4.53 ± 1.29 57 4.55 ± 1.42 .94
  Fasting triglycerides in mmol/L, mean ± SD 51 2.45 ± 1.90 58 2.56 ± 1.62 .75
  Fasting triglyceride-to-HDL ratio, median (IQR) 51 1.89 (1.15 to 3.14) 57 2.00 (1.26 to 4.28) .43
  Fasting glucose in mmol/L, mean ± SD 26 5.14 ± 1.14 42 4.98 ± 0.57 .50

Abbreviations: SD, standard deviation; IQR, interquartile range; BMI, body mass index; LDL, low-density lipoprotein; HDL, high-density
lipoprotein.

obligatory covariates to adjust for potential confounding
related to change in adiposity and lifestyle. Finally, we
used univariable linear regression models adjusted for
repeated measures again through a compound symmetry
covariance structure to identify nonpharmacological
factors associated with increased TG levels. All statisti-
cal analyses were performed using SAS statistical soft-
ware version 9.3 (SAS Institute, Cary, NC).
Results
Patient characteristics and medical status at presentation
are reported in Table 1 with stratification based on those
receiving fish oil (n = 60) at any time during subsequent
follow-up versus those never receiving fish oil (n = 51).
With the exception of a higher proportion of patients
with a history of diabetes mellitus in the no fish oil
group, there were no differences between patients who
subsequently received fish oil versus those patients who
never received fish oil. A total of 651 clinical assess-
ments were reviewed for analysis.
Of the 175 clinical assessments for patients currently
on fish oil, 10 patients for a total of 24 assessments
received 1000 mg/d of fish oil, while the remainder (50
patients, 151 assessments) received a lower dose of 500
mg/d. The proportion of patients who were ever pre-
scribed statins was similar between groups with 5/51
(10%) in the no fish oil group and 9/60 (15%) in the fish
oil group (P = .57). Use of other lipid-lowering medica-
tion was limited. Fibrates (Lipidil) were prescribed to 2
patients (1 in each group). Ezetimibe (fish oil group) and
bile acid sequestrant (no fish oil group) were each pre-
scribed to 1 patient. Fish oil in this context was found to
be well tolerated and accepted by families with noncom-
pliance from self-report as noted in medical records in
only 5/60 (8%) patients.

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648 Clinical Pediatrics 53(7)
Figure 2.  Change in lipid profile of hypertriglyceridemic
patients associated with treatment with fish oil and/or
statins. All lipid values are reported in mmol/L. Dashed
black bars represent effect of statin treatment, while gray
represent fish oil.
Abbreviations: LDL, low-density lipoprotein; HDL, high-density
lipoptorein.
Regression models adjusted for repeated measures
and time since referral, age at assessment and baseline
lipid profile were used to determine the concurrent
effect of fish oil and statins on fasting lipid profiles. As
expected, treatment with statins was associated with a
reduction in LDL cholesterol, non-HDL cholesterol,
and total cholesterol but not in any other parameters of
the lipid profile. Treatment with fish oil was associated
with a clinically important but not statistically signifi-
cant decrease in TGs and TG-to-HDL ratio, but was not
associated with changes in other parameters of the lipid
profile (Figure 2). All associations remained unchanged
when adjusted for BMI z score, nutrition, physical
activity, and screen time. Nonpharmacological factors
associated with higher TG levels in this population
were higher cholesterol levels (total cholesterol, non-
HDL-cholesterol), lower HDL-C, higher baseline TG
level, higher BMI z score/waist-to-height ratio, higher
blood pressure z score, and shorter time since referral
(Table 2).
Discussion
This retrospective study examined the effectiveness of
fish oil supplementation in a high-risk pediatric popula-
tion with dyslipidemia being followed in a specialized
lipid disorder clinic. Among these patients with elevated
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TG (≥1.5 mmol/L), we recommended patients to start
nonprescription fish oil supplementation at an age-
dependent dose of 500 mg/d (<10 years old) or 1000
mg/d (≥10 years old). Approximately 50% of children
decided to take fish oil supplementation. In terms of the
fasting lipid profile at baseline, there were no significant
differences between patients who never received fish oil
compared with those who were currently on fish oil,
with the exception of higher TG levels. A likely explana-
tion for this observation is that fish oil is typically not
suggested to patients until TG levels reach a certain cut-
off point.
Lifestyle modification in adults has been shown to be
effective in lowering TG levels by 20% to 30%.2
Treatment with fibrates or niacin is known to improve
TG levels by 20% to 50% and HDL-C levels by 10% to
35% in pharmacotherapy trials.23 In a study of patients
with type 2 diabetes mellitus and combined hyperlip-
demia, a combination of statins and fibrates was shown
to decrease LDL-C by 46%, decrease TG by 50%, and
increase HDL-C by 22%.24 Prescription omega-3 fatty
acid preparations (eg, Omacor or Lovaza) are recom-
mended for severe hypertriglyceridemia in adults (≥500
mg/dL or 5.6 mmol/L)25 and have shown to decrease TG
levels up to 45%.26 Nonprescription, over-the-counter
dietary supplements of omega-3 fatty acids have been
reported to achieve 10% to 30% reduction in TG lev-
els.27 For cases of isolated hypertriglyceridemia, fish oil
supplementation may be started as the sole line of treat-
ment or incorporated to augment a fibrate regimen.28
There are limited published data reported on concomi-
tant lifestyle modification and use of TG-lowering med-
ications. No prospective studies with prescription
omega-3 or fish oil have been performed in children for
the management of hypertriglyceridemia; therefore, a
conservative approach based on adult dosage was fol-
lowed for the dosage in our clinic.
The hypotriglyceridemic effect of fish oil has been
attributed to its omega-3 fatty acid content, which has
been described through kinetic studies in humans and
animals.29,30 However, the exact mechanism responsible
for the TG-lowering properties of omega-3 fatty acid in
humans remains unclear. It has been postulated that
omega-3 fatty acid can impair the synthesis of TGs
through either decreasing the availability of substrates
(ie fatty acids), amplifying the synthesis of phospholip-
ids, or lowering the activity of enzymes involved in the
synthesis of TGs.30 Decreased lipogenesis and increased
β-oxidation are frequently observed within animal stud-
ies related to omega-3 fatty acid feeding.30
Along with hypertriglyceridemia, a number of the
aforementioned variables contribute to the diagnosis of
metabolic syndrome, which together heightens the risk
Chahal et al 649

Table 2.  Nonpharmacological Factors Associated With Increased Triglyceride Levels.

Variable Effect size (95% CI) Unit Reference P

Higher TC level +0.23 (+0.12, +0.34) mmol/L TG per 1.0 mmol/L TC <.001
Lower HDL-cholesterol level −0.20 (−0.28, −0.11) mmol/L TG per 0.1 mmol/L HDL <.001
Higher non-HDL-cholesterol level +0.29 (+0.14, +0.45) mmol/L TG per 1.0 mmol/L non-HDL <.001
Higher baseline TG level +0.39 (+0.30, +0.47) mmol/L TG per 1.0 mmol/L baseline TG <.001
Higher BMI z score +0.30 (+0.13, +0.47) mmol/L TG per +1.0 BMI z score .001
Higher pulse pressure +0.14 (+0.06, +0.21) mmol/L TG per 10 mm Hg .001
Higher diastolic blood pressure +0.12 (+0.02, +0.23) mmol/L TG per +1.0 diastolic blood .02
z score pressure z score
Shorter time since referral −0.10 (−0.18, −0.02) mmol/L TG per 1.0 year since referral .02
Greater waist-to-height ratio +0.27 (+0.01, +0.53) mmol/L TG per 0.1 .05

Abbreviations: CI, confidence interval; TC, total cholesterol; TG, triglycerides; HDL, high-density lipoprotein; BMI, body mass index.

for diabetes and CVD.31-33 There is limited information
available about elevated TGs levels and cardiovascular
risks in children. Nevertheless, pathological data from
several studies,34,35 including a meta-analysis of 17 pro-
spective trials7 reported that elevated levels of TG dou-
bles the risk of cardiovascular disease in comparison to
those with normal levels. In addition to low concentra-
tions of TGs,6,7 high levels of HDL-C have been previ-
ously reported to reduce the risk of CVD.36,37
Elevated plasma TG concentration is a common bio-
chemical finding associated with pediatric obesity.38
Pediatric dyslipidemia is an established risk factor for
atherosclerosis in adults.4 Specific data are lacking
about the association between pediatric hypertriglyceri-
demia and future cardiovascular risk, and evidence of
benefit associated with treating hypertriglyceridemia
remains less robust than that for treating elevated LDL-
C.39 Part of the difficulty in reaching specific recom-
mendations has been the frequent coexistence of
elevated TGs with other conditions that affect CVD risk,
such as decreased HDL-C, obesity, metabolic syndrome,
pro-inflammatory and pro-thrombotic biomarkers, and
type-2 diabetes.16
Our results are equivocal with regard to the associa-
tion between fish oil supplementation and improved
lipid profile in pediatric patients with hypertriglyceride-
mia. In a comprehensive review, Harris27 reported that
≈4 g/d of omega-3 fatty acids from fish oil decreased
serum TG concentrations by 25% to 30%, with accom-
panying increases in LDL-C of 5% to 10% and in
HDL-C of 1% to 3%. A dose–response relationship
exists between omega-3 fatty acid intake and TG reduc-
tion. Postprandial triglyceridemia is especially sensitive
to chronic omega-3 fatty acid consumption.40,41 with
quite small intakes (>2 g/d) producing significant reduc-
tions.42 Effective doses of omega-3 fatty acids range
from 3 to 5 g/d, which can only be obtained consistently
by supplementation.
The findings of the present study must be interpreted
in light of the limitations including the retrospective
design which limited the amount of available data and
the nonrandom assignment of fish oil supplementation.
While statistical strategies were used to minimize con-
founding as much as possible, confounder effects cannot
be excluded. Physical activity, screen time, nutrition,
and compliance with fish oil supplementation were self-
reported and might not be entirely accurate.
Conclusion
In conclusion, nonprescription fish oil supplementation
was not significantly effective in treating hypertriglyc-
eridemia in pediatric patients in the clinical setting,
although it was well accepted.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) disclosed receipt of the following financial sup-
port for the research, authorship, and/or publication of this
article: This study was supported in part by the CIBC World
Markets Children’s Miracle Foundation endowed Chair in
Child Health Research.
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