You are on page 1of 8



PENXXX10.1177/0148607114549253Journal of Parenteral and Enteral NutritionMateu-de Antonio and Florit-Sureda

Brief Communication

New Strategy to Reduce Hypertriglyceridemia During

Parenteral Nutrition While Maintaining Energy Intake

Javier Mateu-de Antonio, PharmD1; and Marta Florit-Sureda, PharmD1

Journal of Parenteral and Enteral

Volume 40 Number 5
July 2016 705712
2014 American Society
for Parenteral and Enteral Nutrition
DOI: 10.1177/0148607114549253
hosted at

Background: Hypertriglyceridemia is a frequent metabolic complication associated with fat administration in parenteral nutrition (PN).
No clear guidelines have been published on how to proceed once hypertriglyceridemia has been detected. A new strategy could be
to substitute the initial fat emulsion with another emulsion with faster clearance. Our objective was to determine the effectiveness
in reducing triglyceridemia values, maintaining the caloric intake, and improving nutrition parameters in patients who had moderate
hypertriglyceridemia during PN when an olive oilbased fat emulsion (OOFE) was substituted with a multiple-source oil fat emulsion
(MOFE). We also assessed the safety of this substitution in hepatic and glycemic profiles. Materials and Methods: We performed a
retrospective, observational study that included 38 adult patients to whom OOFE in PN was substituted with MOFE when moderate
hypertriglyceridemia (250400 mg/dL) was detected. Results: Triglyceridemia values decreased in 36 (94.7%) patients. The mean
reduction was 71 (8822) mg/dL. Fat load was slightly reduced after substitution (0.14 [0.23 to 0] g/kg/d; P < .001), but total caloric
intake increased from 22.5 (19.725.1) to 23.1 (19.826.8) kcal/kg/d (P = .053). After substitution, nutrition parameters improved, liver
parameters remained unchanged, and insulin requirements increased. Conclusion: The substitution of OOFE with MOFE in patients with
moderate hypertriglyceridemia during PN resulted in a reduction in triglyceridemia values of about 70 mg/dL. That allowed maintaining
the caloric intake and improved nutrition parameters without affecting the hepatic profile. For some patients, insulin requirements
increased moderately. (JPEN J Parenter Enteral Nutr. 2016;40:705-712)

energy intake; hypertriglyceridemia; intravenous fat emulsion; olive oil; parenteral nutrition; plant oils

Clinical Relevancy Statement

Moderate hypertriglyceridemia during parenteral nutrition
often leads to decreased fat administration and energy intake,
although no clear guidelines have been published on this topic.
Our study, applicable in the clinical setting, presented a new
strategy to improve hypertriglyceridemia while maintaining
energy intake without worsening liver or glycemic profiles.

Hypertriglyceridemia is a frequent metabolic complication
associated with fat administration in parenteral nutrition (PN).
Its incidence ranges from 6%38%.1
Hypertriglyceridemia occurs if the infusion rate exceeds the
capacity of plasma fat clearance. Several factors are known to
increase its risk during PN. They include renal failure, sepsis,
pancreatitis, hyperglycemia, high-output enterocutaneous fistulas, diabetes, obesity, alcoholism, multiple organ failure, and
administration of certain drugs such as corticosteroids, cyclosporine, tacrolimus, sirolimus, propofol, or glucose.2,3 No clear
guidelines have been published on how to proceed once hypertriglyceridemia during PN has been detected. Fat withdrawal
has been proposed at different triglyceridemia values (eg, >400
mg/dL,4,5 >440 mg/dL,6 >500 mg/dL,7 or even >1000 mg/dL8).
At lower plasma levels, a fat dose reduction has been

proposed,6-8 but this reduction has not been defined. Reduction

or withdrawal of the fat content in PN usually reduces the
energy provided; due to fat calories lost, this cannot be fully
compensated by increasing the rest of macronutrients.
Different fat emulsions have a different plasma clearance.
The substitution of the fat emulsion causing hypertriglyceridemia with another emulsion with faster clearance could be a
strategy to manage this situation.
The primary aim of the present study was to determine the
effectiveness in reducing triglyceridemia values, maintaining
the caloric intake, and improving nutrition parameters in
patients with moderate hypertriglyceridemia during PN when
an olive oilbased fat emulsion (OOFE) was substituted with a
multiple-source oil fat emulsion (MOFE). The second aim was
From the 1Pharmacy Department, Hospital del Mar, Barcelona, Spain.
Financial disclosure: None declared.
Conflicts of interest: None declared.
Received for publication March 4, 2014; accepted for publication July
12, 2014.
This article originally appeared online on September 11, 2014.
Corresponding Author:
Javier Mateu-de Antonio, PharmD, Pharmacy Department, Hospital del
Mar, Passeig Martim, 25-29, 08003 Barcelona, Spain.

Downloaded from by guest on July 22, 2016


Journal of Parenteral and Enteral Nutrition 40(5)

to evaluate the safety of this substitution by assessing alterations in hepatic and glycemic profiles.

Table 1. Composition of Fat Emulsions Used in the Study.



Study Design

Composition, g/100 mL
Soybean oil
Medium-chain triglycerides
Olive oil
Fish oil
Egg phospholipids
Sodium oleate
Fatty acid content, %
Caprylic acid
Capric acid
Miristic acid
Palmitic acid
Palmitoleic acid
Stearic acid
Oleic acid
Linoleic acid
-Linolenic acid
Arachidonic acid
Eicosapentaenoic acid
Docosahexaenoic acid
Other fatty acids
Ratio -6/-3

We performed a retrospective, observational study at our 400bed, third-level university hospital situated in the urban area of
Barcelona, Spain. The Clinical Research Ethics Committee of
our institution reviewed and approved the study.

Patients and Inclusion and Exclusion

The study included adult patients (18 years old) with individualized PN in which OOFE was substituted with MOFE
when moderate hypertriglyceridemia (250400 mg/dL) was
detected during PN.

Study Period
From September 2009 through March 2013, a total of 38 consecutive patients were included.

PN Support
PN was designed to provide the calculated resting energy
expenditure (REE) by the MifflinSt Jeor equation. In general,
the composition corresponded to 2025 kcal/d, <5 g glucose/
kg/d, <1 g fat/kg/d, and 11.25 g protein/kg/d. The composition was individually modified if necessary according to clinical conditions and laboratory parameters.
PN was prepared following usual hospital practices as an
all-in-one admixture and administered in a 24-hour perfusion. All patients received the same products used to prepare
PN: glucose solutions, standard amino acid solution
(Aminoplasmal L, B.Braun, Rub, Spain), OOFE (Clinoleic
20%; Baxter Clintec, Maurepas, France), MOFE (SMOFLipid
20%; Fresenius Kabi, Uppsala, Sweden), vitamins (Cernevit;
Baxter Clintec), trace element solution (Addamel; Fresenius
Kabi), and electrolytes. The detailed composition of both fat
emulsions is shown in Table 1.

Intervention was defined as the substitution of OOFE in the PN
with MOFE when the first episode of hypertriglyceridemia
was detected.

Laboratory Determination for


Olive Oil
Based Fat

Source Oil
Fat Emulsion







, nil or negligible value.

a central venous catheter. In the last case, PN infusion was

stopped for 5 minutes, and then a different lumen than the one
used for PN was flushed and the first blood sample discarded
before the valid extraction was obtained. Blood samples were
immediately centrifuged and the supernatant serum separated.
Triglycerides were measured in this supernatant using enzymatic reactions and spectrophotometry.

General Parameters
Data collected from the patients were demographic (sex, age)
and anthropometric (weight, height, body mass index [BMI])
values, REE, type of patient (medical, surgical, trauma),
comorbidities (hypertension, heart failure, cardiovascular disease, stroke, dyslipidemia, diabetes, obesity defined as BMI
between 25 and 35 kg/m2, chronic renal failure, liver disease,
neoplasm, human immunodeficiency virus, alcoholism), severity according to the Charlson index, indication of PN, and
duration of PN.

Risk Factors for Hypertriglyceridemia

Venous blood samples for triglyceride determination were

obtained through a peripheral venous access when possible or

Risk factors for hypertriglyceridemia were sepsis; renal failure

(glomerular filtration rate <60 mL/min/1.73 m2); pancreatitis;
administration of corticosteroids, cyclosporine, tacrolimus,

Downloaded from by guest on July 22, 2016

Mateu-de Antonio and Florit-Sureda


sirolimus, propofol, or glucose solutions; hyperglycemia;

high-output enterocutaneous fistulas; diabetes; obesity; alcoholism; and multiorgan failure.2,3

PN Parameters
Macronutrients and kilocalories provided were collected
before and after the intervention. Date of intervention and date
of next triglyceridemia control were also recorded.

Parameters of Effectiveness
Triglyceridemia, total serum protein, serum albumin, prealbumin,
lymphocytes, and C-reactive protein were recorded at the beginning of PN, before and after the intervention, and at the end of PN.

Parameters of Safety
Alanine aminotransferase (ALAT), aspartate aminotransferase
(ASAT), alkaline phosphatase, -glutamyl transferase (GGT),
and total bilirubin were recorded as parameters of liver toxicity
at the beginning of PN, before and after the intervention, and at
the end of PN.
Hyperglycemia was defined as blood glucose >180 mg/dL.
Days with at least a determination of hyperglycemia, peak of
hyperglycemia, and insulin requirements were calculated
before and after the intervention.

Other Outcomes
Days of PN, length of stay (LOS), and mortality were also

Statistical Analysis
Data were analyzed using the Wilcoxon signed-rank test for
nonparametric paired data, McNemar test to compare paired
proportions, Mann-Whitney U test to compare nonparametric
independent data, and Pearson correlation coefficient to correlate between 2 variables. Data are presented as median values
and quartiles 1 and 3 (Q1Q3).

Table 2. Patient Characteristics.

Age, y
Male sex
Weight, kg
Height, cm
BMI, kg/m2
Calculated resting energy
expenditure, kcal/d
Type of patient: medical/
Charlson index (points)
Chronic renal failure
Heart failurecardiovascular
Obesity (BMI >25 to 35

Median (Q1Q3) or No. (%)

68.0 (60.874.5)
17 (44.7)
68.0 (55.075.0)
164.5 (155.0170.0)
24.0 (22.426.4)
1045 (12681469)
8/29/1 (21.1/76.3/2.6)
5 (48)
20 (52.6)
16 (42.1)
8 (21.1)
7 (18.4)
7 (18.4)
7 (18.4)
6 (15.8)
3 (7.9)
3 (7.9)

BMI, body mass index; Q1, quartile 1; Q3, quartile 3.

(3 [7.9%]), and other (7 [18.4%]). Detailed patient characteristics are shown in Table 2. The indications for PN were postoperative complications in 18 (47.4%) patients, intolerance to
enteral nutrition or inability to have enteral access in 7 (18.4%),
intestinal obstruction in 4 (10.5%), intestinal ischemia in 3
(7.9%), protocolled postoperative fasting in 3 (7.9%), and
other indications in 3 (7.9%).
Nutrition and biochemical parameters at the beginning of
PN are shown in Table 3. As main features, patients had a moderate inflammatory state with severe hypoalbuminemia and
low prealbuminemia. Median triglyceridemia values were
within the high side of the normal range, and liver parameters
were normal except for GGT, which was mildly elevated.

Triglyceridemia and PN
Forty-seven patients were initially selected for the study. Nine
patients were later excluded5 for basal triglyceridemia values
>250 mg/dL, 3 for mixed nutrition, and 1 for BMI 35 kg/m2
resulting in a total of 38 patients. Most patients were women,
with an average age of 68 years, with a BMI in the normal
range, a Charlson index moderately high, and a high rate of
hypertension, neoplasm, and diabetes. Patients were admitted
in the departments of surgery (21 [55.3%]), urology
(4 [10.5%]), oncology (3 [7.9%]), surgical intensive care unit

The episode of hypertriglyceridemia was detected at day 8

(613) from the beginning of PN. Thirty-three (86.8%) patients
had 1 or more risk factors for hypertriglyceridemia at the
beginning of PN: 17 (44.7%) had only 1 risk factor, 6 (15.8%)
had 2 risk factors, 6 (15.8%) had 3 risk factors, and 4 (10.5%)
had more than 3 risk factors. In 5 (13.2%) patients, no risk factors could be established. The main risk factors were hyperglycemia in 11 (28.9%) patients, renal failure in 9 (23.7%), sepsis
in 8 (21.1%), administration of corticosteroids in 8 (21.1%),
diabetes in 8 (21.1%), glucose solutions external to PN in 8
(21.1%), obesity in 6 (15.8%), pancreatitis in 3 (7.9%), and
other causes in 7 (18.4%).

Downloaded from by guest on July 22, 2016


Journal of Parenteral and Enteral Nutrition 40(5)

Table 3. Nutrition and Biochemical Parameters at the Beginning

of Parenteral Nutrition.
Triglyceridemia, mg/dL
Total serum proteins, g/dL
Serum albumin, g/dL
Prealbumin, mg/dL
Lymphocytes, 103 cell/mL
Glycemia, mg/dL
Total bilirubin, mg/dL
Alkaline phosphatase, U/L
C-reactive protein, mg/dL


Normal Range

146 (120194)
5.0 (4.15.5)
2.4 (1.92.6)
12.1 (8.716.3)
0.9 (0.71.5)


115 (88134)
0.4 (0.30.7)
20 (1432)
20 (1133)
94 (43159)
107 (73177)
9.9 (4.622.8)


ALAT, alanine aminotransferase; AST, aspartate aminotransferase; GGT,

-glutamyl transferase; Q1, quartile 1; Q3, quartile 3.

Risk factors for hypertriglyceridemia during the MOFE

course presented several changes from the initial profile.
Glycemia increased in 15 (39.5%) patients and decreased in 4
(10.5%). Renal failure improved in 6 (15.8%) patients and
worsened in 2 (5.3%). Sepsis improved in 7 (18.4%) patients,
and 4 (10.5%) patients developed new septic episodes. Doses
of corticosteroids were increased in 2 (5.3%) patients and
decreased in 2 (5.3%). Patients with glucose solutions external
to PN were reduced to 2 (5.3%), and these solutions accounted
for 3% of total glucose load. No patient developed a new pancreatitis episode during PN. When analyzed globally, in 21
(55.3%) patients, 23 changes favored hypertriglyceridemia,
and in 17 (44.7%) patients, 21 favored a decline in blood triglyceride levels.
Data regarding macronutrients and calories provided before
and after the intervention are shown in Table 4. After the intervention, the amounts of protein and glucose increased and fat
decreased. Fat load was decreased in 26 (68.4%) patients. The
kilocalories provided and the kcal/REE ratio did not vary.
However, these last 2 parameters had a trend to higher values
after the intervention.

The subsequent control of triglyceridemia was done on day 7
(48) after the intervention, corresponding to day 15 (1019)
from the beginning of PN. Nutrition and biochemical parameters before and after the intervention are shown in Table 5. The
variation in triglyceridemia values before and after the intervention did not correlate with the variation in fat provided
daily (P = .773) or fat provided by kilogram daily (P = .775).
Triglyceridemia values before the intervention did not

correlate with the variation in triglyceridemia values before

and after the intervention (P = .598) either.
Triglyceridemia values decreased in 36 (94.7%) patients
after the substitution of the fat emulsion. No differences were
detected (P = .566) in the decrease of triglyceridemia values
among patients to whom fat load was decreased (26 [68.4%])
or maintained (12 [31.6%]). Nutrition parameters such as total
serum proteins, serum albumin, and prealbumin increased.
After the postintervention period, additional triglyceridemia controls were present in 18 (47.4%) patients in whom PN
was continued. Of these patients, 13 (34.2%) maintained
MOFE and 5 (13.2%) reverted to OOFE.
In the 13 patients remaining on MOFE, triglyceridemia values increased in 5 (38.5%) and decreased in 8 (61.5%) in the
subsequent control, day 7 (58) from the prior control, corresponding to day 24 (1930) from the beginning of PN.
Triglyceridemia values reached 223 (181249) mg/mL at this
time, corresponding to a variation of 7 (26 to 26) mg/dL
from the preceding control (P = .529). The fat load was
increased by 0.10 (0.020.22) g/kg/d from the postintervention
period (P = .011).
All 5 (100%) patients who reverted to OOFE had increased
triglyceridemia values in the subsequent control, day 6 (49)
of the new OOFE course, corresponding to day 21 (1632)
from the beginning of PN. Their triglyceridemia values
reached 289 (215343) mg/dL, corresponding to an increase
of 88 (55148) mg/dL from the preceding control during
MOFE administration (P = .043). The fat load of OOFE did
not change from the previous MOFE course (P = .500). Both
groups differed in the proportion of patients who had increased
triglyceridemia values (P = .036) and for those with triglyceridemia variation (P = .004), with these values being higher for
the OOFE-reverted group in both cases (see Figure 1). Three
of these 18 patients had further changes in their fat emulsions
before the end of the PN.

Liver parameters did not change after intervention (see Table
5). Nineteen (50%) patients had hyperglycemia before the
intervention and 15 (39.5%) had hyperglycemia after the intervention (P = .219). The peak of hyperglycemia was 233 (201
261) mg/dL preintervention and 223 (200276) mg/dL
postintervention, without differences between them (P = .394).
Insulin requirements in these patients were 0.12 (0.04 0.22)
IU/kg/d preintervention and increased to 0.26 (0.110.34) IU/
kg/d postintervention (P = .006). At the end of PN, triglyceridemia values, nutrition parameters, and liver parameters did
not change from postintervention values (data not shown).

PN lasted 21.0 (12.039.0) days. LOS was 48.0 (23.869.5)
days, and 5 (13.2%) patients died during admission.

Downloaded from by guest on July 22, 2016

Mateu-de Antonio and Florit-Sureda


Table 4. Macronutrients and Total Kilocalories Provided Before and After Intervention.
Protein, g/d
Protein load, g/kg/d
Glucose, g/d
Glucose load, g/kg/d
Fat, g/d
Fat load, g/kg/d
Total kcal/d
Total kcal/kg/d
Ratio total kcal/REE

Preintervention, Median

Postintervention, Median

Variation, Median

P Value

76.1 (58.7 to 87.5)

1.13 (1.03 to 1.24)
190 (165 to 209)
2.45 (2.85 to 3.23)
40 (37 to 50)
0.68 (0.54 to 0.77)
1497 (1295 to 1699)
22.5 (19.7 to 25.1)
1.18 (1.06 to 1.28)

79.8 (69.9 to 87.5)

1.17 (1.09 to 1.34)
217 (181 to 250)
3.33 (2.87 to 3.71)
34 (26 to 40)
0.53 (0.43 to 0.66)
1524 (1342 to 1701)
23.1 (19.8 to 26.8)
1.21 (1.11 to 1.31)

4.2 (4.1 to 11.6)

0.06 (0.06 to 0.19)
31.4 (9.3 to 40.9)
0.51 (0.17 to 0.68)
9.8 (16.0 to 0)
0.14 (0.23 to 0)
27 (62 to 190)
0.4 (1.0 to 3.1)
0.02 (0.06 to 0.16)


Q1, quartile 1; Q3, quartile 3; REE, resting energy expenditure.

Table 5. Nutrition and Biochemical Parameters Before and After Intervention.

Triglyceridemia, mg/dL
Total serum proteins, g/dL
Serum albumin, g/dL
Prealbumin, mg/dL
Lymphocytes, 103 cell/mL
Total bilirubin, mg/dL
Alkaline phosphatase, U/L
C-reactive protein, mg/dL

Preintervention, Median

Postintervention, Median

Variation, Median

P Value

295 (251 to 333)

5.1 (4.6 to 5.9)
2.2 (1.9 to 2.7)
16.6 (11.0 to 23.2)
1.14 (0.86 to 1.65)

222 (176 to 276)

5.5 (4.8 to 6.4)
2.6 (2.1 to 3.1)
23.7 (12.8 to 30.8)
1.20 (0.91 to 1.51)

71 (88 to 22)
0.3 (0.2 to 1.0)
0.2 (0 to 0.5)
4.7 (0.7 to 12.1)
0.05 (0.32 to 0.41)

0.3 (0.2 to 0.7)

26 (18 to 44)
25 (13 to 61)
238 (180 to 327)
183 (110 to 429)
5.9 (1.2 to 20.1)

0.4 (0.2 to 0.8)

23 (18 to 43)
33 (16 to 57)
363 (205 to 700)
232 (135 to 405)
5.9 (2.4 to 11.7)

0 (0 to 0.2)
1 (17 to 8)
0 (11 to 11)
19 (71 to 170)
3 (62 to 44)
0.3 (5.7 to 3.4)


ALAT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, -glutamyl transferase; Q1, quartile 1; Q3, quartile 3.

To our knowledge, this is the first study assessing the effectiveness and safety of substituting a fat emulsion for hypertriglyceridemia during PN. The substitution of OOFE with MOFE for
patients with moderate hypertriglyceridemia during PN was an
effective strategy in reducing triglyceridemia values, maintaining caloric intake, and improving nutrition parameters without
affecting patients liver and glycemic profiles.
At our institution, MOFE containing -3 fatty acids was
initially protocolled for critically ill patients receiving PN with
a high level of systemic inflammation, while OOFE was used
in the rest of the patients. We had surprisingly detected lower
triglyceridemia values in many critically ill patients than in
noncritically ill patients. In view of those findings, we decided
to use MOFE in cases of hypertriglyceridemia in noncritically
ill patients.
Around 85% of our patients had risk factors for hypertriglyceridemia. Some of these factors changed during the PN

course. Hyperglycemia was the main factor before PN was

started. At the beginning of PN, basal glycemia was marginally
higher than normal (see Table 3). Before hypertriglyceridemia
was detected, 50% of patients had at least a peak of hyperglycemia. Glucose and fat provided in PN possibly contributed in
some degree to the development of hypertriglyceridemia in
these patients. However, the glucose load was moderate (see
Table 4). It accounted for <2 mg/kg/min, the recommended
dose for patients at risk for hyperglycemia.7 The rest of the factors for hypertriglyceridemia also changed during PN. More
than the half of patients still developed factors that favored
hypertriglyceridemia during the intervention period. Another
factor to be considered was the change in inflammation level.
C-reactive protein decreased from the basal value, but it did
not change during the pre- and postintervention period (see
Table 5). However, triglyceridemia values decreased in most
patients, indicating that the change in the fat emulsion, the last
factor to take into account, had played a role in this decrease.
This could be reinforced by the fact that triglyceridemia values

Downloaded from by guest on July 22, 2016


Journal of Parenteral and Enteral Nutrition 40(5)

Figure 1. Evolution of triglyceridemia during parenteral nutrition. *Different from basal value (P < .001). Different from preceding
hypertriglyceridemia peak (P < .001). Different variation of triglyceridemia comparing patients continuing with MOFE with patients
reverting to OOFE (P = .004). MOFE, multiple-source oil fat emulsion; OOFE, olive oilbased fat emulsion.

increased again in the 5 patients to whom OOFE was reintroduced after the MOFE course. In comparison, patients maintained on MOFE did not have a change in triglyceridemia
values despite increasing the fat load.
Currently, several fat emulsions are marketed as an alternative to the classic soybean oil fat emulsion (SOFE), mainly in
Europe. SOFE may have deleterious effects due to its high
content of -6 fatty acids, considered to increase the proinflammatory state present in many patients requiring PN.9
Unlike SOFE, those alternative emulsions are composed of fat
from several sources with a lower content of -6 fatty acids.9
Each has a different plasma clearance profile.
In relation to the fat emulsions used in our study, few studies assessed their plasma clearance, mostly in comparison to
SOFE. In 6 young healthy normolipemic participants in a
kinetic precommercialization study,10 OOFE resulted in higher
triglyceridemia values (142%) and in a slower maximum clearance rate (81%) and fractional catabolic rate (61%) compared
with SOFE. This crossover study was performed in experimental conditions with an initial bolus of 0.1 g fat/kg followed by
an infusion of 0.25 g fat/kg/h during 1 hour and without administration of other nutrients. In an early review11 of metabolic
studies mostly in healthy participants, it was concluded that
OOFE in short infusions increased triglyceridemia values in
around 30%, whereas SOFE in short infusions decreased them

in around 30%. However, middle- or long-term infusions did

not differ. Kinetic studies in conditions similar to the usual
clinical settings are lacking. In addition, several clinical studies
included triglyceridemia among the recorded parameters, but it
was not accurately studied. In a retrospective study,12 in 21
patients receiving PN for severe weight loss, triglyceridemia
values increased in 9% of patients who received OOFE compared with 70% of patients who received SOFE, but surprisingly, triglyceridemia values were not reported. In this study,
patients received a dose of fat around 95 g/d despite having a
BMI of 1617 kg/m2. In a prospective study,13 28 patients
receiving PN were randomly assigned 1 of 4 fat emulsions
namely SOFE, OOFE, structured lipid emulsion, or mediumchain/long-chain lipid emulsionfor 5 days. All cohorts had
increased triglyceridemia values, but without differences
among them on the fifth day. Patients received a dose of 1.1
1.2 g fat/kg/d. In a more recent crossover study in 12 healthy
participants,14 in conditions resembling the use of PN for 24
hours, triglyceridemia values increased from basal levels during the use of both emulsions, SOFE and OOFE, but the use of
SOFE presented higher triglyceridemia values after 12 hours
than did the use of OOFE. The actual fat dose that patients
received was not clearly stated in this study. In another comparative study in which 20 patients underwent abdominal surgery for cancer and received PN,15 triglyceridemia values

Downloaded from by guest on July 22, 2016

Mateu-de Antonio and Florit-Sureda


increased by 9.4 mg/dL in the cohort that received SOFE and

decreased by 11.2 mg/dL in the cohort that received OOFE
during the first week, but this difference was not statistically
significant. The dose of fat that patients received was intended
to be 0.75 g/kg/d.
MOFE clearance was tested in a phase I crossover study.16
Twelve healthy participants received 0.125 g fat/kg/h for 6
hours of SOFE and MOFE in 2 separate infusions.
Triglyceridemia values were lower by 73% after MOFE infusion compared with the SOFE infusion. Triglyceride half-life
was significantly lower for MOFE (34 11 min) than for
SOFE (59 25 min). Three randomized studies in patients
receiving PN assessed the evolution of triglyceridemia for
MOFE compared with SOFE, among other parameters studied.
In the first study in 20 critically ill surgical patients after 6 days
of PN,17 the cohort that received SOFE had statistically significant increased triglyceridemia values of around 100 mg/dL,
whereas the cohort that received MOFE did not have increases
in this parameter. The patients received 1.5 g fat/kg/d. In the
second study in 199 surgical patients,18 both cohorts (those
who received SOFE or MOFE) had slowly increased triglyceridemia values during the 5 days of the study but without differences between them. Patients received 1.5 g fat/kg/d. In the
last study on safety and tolerance in 73 patients who required
PN for 4 weeks,19 triglyceridemia values remained stable and
were not statistically different between the cohorts that received
MOFE or SOFE. However, triglyceridemia values in the
MOFE cohort were lower than those in the SOFE cohort in all
points measured. The fat dose delivered was 1.3 g/kg/d.
Only 1 study compared the 2 emulsions used in our study
in adult patients with the objective of liver integrity. In this
randomized study in 44 postoperative patients,20 the cohort
that received OOFE had a triglyceridemia of 51 mg/dL higher
at the second day and 70 mg/dL higher at the fifth day of PN
than the cohort that received MOFE. Patients received around
1 g fat/kg/d.
Considering all these studies, OOFE seemed to be cleared
similarly or slightly slower than SOFE, and MOFE seemed to be
cleared faster than SOFE. Thus, OOFE seemed to be cleared
slower than did MOFE. The study that compared directly both
emulsions seemed to confirm this point.20 Olive oil has a lower
uptake by the reticuloendothelial system and lower removal
capacity by hepatic lipases than does soybean oil.10 Moreover,
pure fish oils are inefficiently cleared by hepatic lipases, but surprisingly, when they are incorporated in a minor proportion in
other lipid emulsions, they enhance the fat clearance by increasing the removal of remnant fat particles by endocytosis.21
For our patients, the difference in triglyceridemia values was
also very close to that seen in this last study, around 70 mg/dL.
In addition, MOFE contains -3 fatty acids, which could maximize the reduction in triglyceridemia since these fatty acids
have shown to be effective in treating hypertriglyceridemia.22
In our patients, the substitution of fat emulsion was safe in
relation to liver profile since we did not detect any alterations
of hepatic markers postintervention. Both fat emulsions we

used have been considered safer than SOFE in relation to

hepatic complications and have been proposed as an alternative.12,17,19,23 However, in a head-to-head study, the cohort that
received MOFE presented lower plasma values of alanine aminotransferase, aspartate aminotransferase, and -glutathione
S-transferase, an early marker of hepatic injury.20 That could
indicate that our intervention would even reduce the risk of
hepatic alteration, especially if the fat dose maintained is lower
than 1 g/kg/d. This dose has been recommended for minimizing hepatic dysfunction in adults receiving PN.23 After the
intervention, our patients received less fat (a decrease of 0.14 g
fat/kg/day, corresponding to 10 g fat/day) and more glucose
(an increase of 0.51 g glucose/kg/day, corresponding to 30 g
glucose/day), but these variations seemed of little clinical relevance. Interestingly, patients with reduction of fat load after
the intervention and those without reduction presented a similar decline in hypertriglyceridemia values. However, the moderate increase of glucose in PN could be theoretically
disadvantageous for fat clearance since, in experimental conditions, lipoprotein lipase activity decreases after glucose administration.24 In contrast, in clinical conditions of PN, fat
clearance is not altered by glucose infusion,25 or alternative
routes of fat clearance are present.26 On the other hand, sustained hypertriglyceridemia and the concomitant increase of
free fatty acids could predispose to an impaired glucose tolerance.27,28 In our patients, the insulin requirements increased
after the intervention, but possibly this was due to the hypertriglyceridemic state they presented, at least in part, rather than to
the increase in glucose load.
Management of hypertriglyceridemia during PN has no wellstudied strategies, aside from the decrease or the discontinuation
of fat provision depending on the plasma lipid level.4-8 Several
nutrients or drugs have been considered in this situation, but none
currently has a good level of evidence. Carnitine supplementation in PN is not routinely recommended in adult patients with
hypertriglyceridemia.29 Heparin activates lipoprotein lipase, but
its use in adult PN is not recommended. While heparin can
increase lipolysis from infused emulsions, it can also increase
plasma free fatty acids and their reesterification, but it does not
affect their oxidation.30 Pravastatin, gemfibrozil, and atorvastatin
increased fat plasma clearance in dyslipemic patients in an experimental intravenous infusion of chylomicrons-like fat emulsions,31-33 but these studies have not been transferred to patients
requiring PN. In addition, these drugs, which have only oral formulations, seem unsuitable for patients requiring PN who are
under a nil per os instruction in most cases.
Our study had several limitations. First, it was a retrospective study. Therefore, the effect of MOFE could not be accurately assessed, but it establishes the basis for a randomized
controlled trial to evaluate the actual effect of this fat emulsion.
Moreover, the number of patients was limited, but it was in the
range of other studies on this topic.12,13,15,17,20 In addition, it has
to be taken into account that patients in our study were their
own controls postintervention. Last, we did not study the effect
of other fat emulsions and did not know if a reduction in

Downloaded from by guest on July 22, 2016


Journal of Parenteral and Enteral Nutrition 40(5)

hypertriglyceridemia could be obtained in other situations.

However, it seemed plausible that a hypertriglyceridemia
reduction could be obtained with the substitution of SOFE with
MOFE, since SOFE is cleared similarly or slightly faster than
OOFE but slower than MOFE.
In conclusion, the substitution of OOFE with MOFE in
patients with moderate hypertriglyceridemia during PN
resulted in a reduction in triglyceridemia values of 70 mg/dL.
That allowed maintaining the caloric intake and improved
nutrition parameters without affecting hepatic parameters and
only with a moderate increase in insulin requirements.

Statement of Authorship
J. Mateu-de Antonio contributed to the conception/design of the
research. J. Mateu-de Antonio and M. Florit-Sureda contributed to
the acquisition, analysis, and interpretation of the data; drafted the
manuscript; critically revised the manuscript; agree to be fully
accountable for ensuring the integrity and accuracy of the work;
and read and approved the final manuscript.

1. Mirtallo JM, Dasta JF, Kleinschmidt KC, Varon J. State of the art review:
intravenous fat emulsions: current applications, safety profile, and clinical
implications. Ann Pharmacother. 2010;44(4):688-700.
2. Llop J, Sabin P, Garau M, et al. The importance of clinical factors
in parenteral nutritionassociated hypertriglyceridemia. Clin Nutr.
3. Visschers RG, Olde Damink SW, Schreurs M, Winkens B, Soeters PB,
van Gemert WG. Development of hypertriglyceridemia in patients with
enterocutaneous fistulas. Clin Nutr. 2009;28(3):313-317.
4. Visschers RG, Olde Damink SW, Gehlen JM, Winkens B, Soeters PB,
van Gemert WG. Treatment of hypertriglyceridemia in patients receiving
parenteral nutrition. JPEN J Parenter Enteral Nutr. 2011;35(5):610-615.
5. Btaiche IF, Khalidi N. Metabolic complications of parenteral nutrition in
adults, part 1. Am J Health Syst Pharm. 2004;61(18):1938-1949.
6. Braga M, Ljungqvist O, Soeters P, et al. ESPEN guidelines on parenteral
nutrition: surgery. Clin Nutr. 2009;28(4):378-386.
7. Sacks GS, Mayhew S, Johnson D. Parenteral nutrition implementation and
management. In: Merritt R, ed. The A.S.P.E.N. Nutrition Support Practice
Manual. 2nd ed. Silver Spring, MD: American Society for Parenteral and
Enteral Nutrition; 2005:108-117.
8. Adolph M, Heller AR, Koch T, et al. Lipid emulsionsguidelines on parenteral nutrition, Chapter 6. Ger Med Sci. 2009;7:Doc22.
9. Calder PC. Hot topics in parenteral nutrition: rationale for using new lipid
emulsions in parenteral nutrition and a review of the trials performed in
adults. Proc Nutr Soc. 2009;68(3):252-260.
10. Brouwer CB, de Bruin TW, Jansen H, Erkelens DW. Different clearance
of intravenously administered olive oil and soybean-oil emulsions: role of
hepatic lipase. Am J Clin Nutr. 1993;57(4):533-539.
11. Beaufrre B. Efficacit nutritionnelle et mtabolique de ClinOlic 20%.
Nutr Clin Metab. 1996;10(4)(suppl):29S-31S.
12. Palova S, Charvat J, Kvapil M. Comparison of soybean oil and olive
oilbased lipid emulsions on hepatobiliary function and serum triacylglycerols level during realimentation. J Int Med Res. 2008;36(3):587-593.
13. Puiggros C, Sanchez J, Chacon P, et al. Evolution of lipid profile, liver
function, and pattern of plasma fatty acids according to the type of
lipid emulsion administered in parenteral nutrition in the early postoperative period after digestive surgery. JPEN J Parenter Enteral Nutr.

14. Siqueira J, Smiley D, Newton C, et al. Substitution of standard soybean oil

with olive oilbased lipid emulsion in parenteral nutrition: comparison of
vascular, metabolic, and inflammatory effects. J Clin Endocrinol Metab.
15. Onar P, Yildiz BD, Yildiz EA, Besler T, Abbasoglu O. Olive oilbased
fat emulsion versus soy oil-based fat emulsion in abdominal oncologic
surgery. Nutr Clin Pract. 2011;26(1):61-65.
16. Schlotzer E, Kanning U. Elimination and tolerance of a new parenteral
lipid emulsion (SMOF)a double-blind cross-over study in healthy male
volunteers. Ann Nutr Metab. 2004;48(4):263-268.
17. Antebi H, Mansoor O, Ferrier C, et al. Liver function and plasma antioxidant status in intensive care unit patients requiring total parenteral nutrition: comparison of 2 fat emulsions. JPEN J Parenter Enteral Nutr. 2004;28(3):142-148.
18. Mertes N, Grimm H, Furst P, Stehle P. Safety and efficacy of a new parenteral lipid emulsion (SMOFlipid) in surgical patients: a randomized,
double-blind, multicenter study. Ann Nutr Metab. 2006;50(3):253-259.
19. Klek S, Chambrier C, Singer P, et al. Four-week parenteral nutrition using
a third generation lipid emulsion (SMOFlipid)a double-blind, randomised, multicentre study in adults. Clin Nutr. 2013;32(2):224-231.
20. Piper SN, Schade I, Beschmann RB, Maleck WH, Boldt J, Rohm KD.
Hepatocellular integrity after parenteral nutrition: comparison of a fishoilcontaining lipid emulsion with an olive-soybean oilbased lipid emulsion. Eur J Anaesthesiol. 2009;26(12):1076-1082.
21. Simoens CM, Deckelbaum RJ, Massaut JJ, Carpentier YA. Inclusion of
10% fish oil in mixed medium-chain triacylglycerol-long-chain triacylglycerol emulsions increases plasma triacylglycerol clearance and induces
rapid eicosapentaenoic acid (20:5n-3) incorporation into blood cell phospholipids. Am J Clin Nutr. 2008;88(2):282-288.
22. McKenney JM, Sica D. Role of prescription omega-3 fatty acids in the treatment of hypertriglyceridemia. Pharmacotherapy. 2007;27(5):715-728.
23. Gabe SM. Lipids and liver dysfunction in patients receiving parenteral
nutrition. Curr Opin Clin Nutr Metab Care. 2013;16(2):150-155.
24. Jindrichova E, Kratochvilova S, Kovar J. Glucose administration downregulates lipoprotein lipase activity in vivo: a study using repeated intravenous fat tolerance test. Physiol Res. 2007;56(2):175-181.
25. Iriyama K, Tsuchibashi T, Urata H, et al. Elimination of fat emulsion particles from plasma during glucose infusion. Br J Surg. 1996;83(7):946-948.
26. Thorne A, Aberg W, Carneheim C, Olivecrona T, Nordenstrom J.
Influence of trauma on plasma elimination of exogenous fat and on lipoprotein lipase activity and mass. Clin Nutr. 2005;24(1):66-74.
27. Carpentier AC, Bourbonnais A, Frisch F, Giacca A, Lewis GF. Plasma
nonesterified fatty acid intolerance and hyperglycemia are associated with
intravenous lipid-induced impairment of insulin sensitivity and disposition index. J Clin Endocrinol Metab. 2010;95(3):1256-1264.
28. Kashyap S, Belfort R, Gastaldelli A, et al. A sustained increase in plasma
free fatty acids impairs insulin secretion in nondiabetic subjects genetically
predisposed to develop type 2 diabetes. Diabetes. 2003;52(10):2461-2474.

29. Borum PR. Carnitine in parenteral nutrition. Gastroenterology.
30. Chen X, Ruiz J, Boden G. Release, oxidation, and reesterification of
fatty acids from infused triglycerides: effect of heparin. Metabolism.
31. Santos RD, Sposito AC, Ventura LI, Cesar LA, Ramires JA, Maranhao RC.
Effect of pravastatin on plasma removal of a chylomicron-like emulsion in
men with coronary artery disease. Am J Cardiol. 2000;85(10):1163-1166.
32. Santos RD, Ventura LI, Sposito AC, Schreiber R, Ramires JA, Maranhao
RC. The effects of gemfibrozil upon the metabolism of chylomicron-like
emulsions in patients with endogenous hypertriglyceridemia. Cardiovasc
Res. 2001;49(2):456-465.
33. Sposito AC, Santos RD, Amancio RF, Ramires JA, Chapman MJ,
Maranhao RC. Atorvastatin enhances the plasma clearance of chylomicron-like emulsions in subjects with atherogenic dyslipidemia: relevance
to the in vivo metabolism of triglyceride-rich lipoproteins. Atherosclerosis.

Downloaded from by guest on July 22, 2016