Clinical Nutrition 42 (2023) 2159e2172

Contents lists available at ScienceDirect

Clinical Nutrition
journal homepage: http://www.elsevier.com/locate/clnu

Original article

Medium-chain triglycerides and the impact on fat absorption, growth,

nutritional status and clinical outcomes in children with cholestatic
liver disease: A scoping review
Sara Mancell a, b, *, Karishma Manwani b, Anil Dhawan c, Kevin Whelan a
a
Department of Nutritional Sciences, King's College London, London, UK
b
Department of Nutrition & Dietetics, King's College Hospital NHS Foundation Trust, London, UK
c
Paediatric Liver, GI and Nutrition, King's College Hospital NHS Foundation Trust, London, UK

a r t i c l e i n f o s u m m a r y

Article history: Background & aims: Medium-chain triglyceride (MCT) supplementation is recommended in cholestatic
Received 14 April 2023 liver disease, despite unclear evidence and no consensus on the ideal percentage of fat that should be
Accepted 10 September 2023 MCT. The aim was to undertake a scoping review to identify the extent and type of evidence regarding
how MCT supplementation, and percentage of MCT, affects fat absorption, growth, nutritional status and
Keywords: clinical outcomes (morbidity, mortality, transplant) in children with cholestatic liver disease.
Absorption
Methods: Nine databases (MEDLINE, Embase, CINAHL, PubMed, AMED, Cochrane Library, Global Health,
Biliary atresia
Scopus, Proquest) were searched from inception, with hand-searching conference abstracts and forward/
Cholestasis
Growth
backward citation searching. Eligible studies investigated oral/enteral MCT supplementation in children
Medium-chain triglycerides under 18y with cholestatic liver disease. There were no language limits. Two reviewers performed
MCT screening and data extraction independently. Data were synthesised narratively.
Results: Following title/abstract screening (1202 studies) and full-text review (40 studies), 24 studies
were included comprising three small RCTs (n ¼ 19 patients), one non-randomised controlled trial
(n ¼ 2), seven uncontrolled trials (n ¼ 83) and thirteen case series/reports (n ¼ 211). Seventeen studies
were published before 1994. Outcomes included absorption, growth and nutritional status. MCT sup-
plementation was associated with greater fat absorption (9/9 studies) and improved growth in some
children (2/4). Higher percentage MCT was associated with greater magnesium and calcium absorption
(1/1), essential fatty acid (EFA) deficiency (4/4), but not growth (3/3).
Conclusions: The limited, mostly observational evidence from >30 years ago points to greater fat ab-
sorption on MCT and EFA deficiency on very high percentage MCT. High quality RCTs are required,
particularly examining the impact of MCT at different percentages on growth, nutritional status and
clinical outcomes.
© 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).

1. Introduction triglycerides (LCT) [1]. Fat is a major source of energy, comprising

Cholestatic liver disease is characterised by reduced bile forma-
tion or bile flow resulting in a depletion of small intestinal bile salts
[1]. The most common causes of cholestatic liver disease in early
childhood are biliary atresia and genetic disorders [2]. One important
nutritional consequence of cholestatic liver disease is impaired fat
absorption as small intestinal bile salts are necessary to facilitate the
emulsification and absorption of fat, specifically long-chain
* Corresponding author. Department of Nutritional Sciences, King's College
London, London, UK.
E-mail address: sara.mancell@kcl.ac.uk (S. Mancell).
40e50% of energy in human milk or formula milk fed to infants [3]
and 20e35% of total dietary energy is recommended in older chil-
dren across Europe [4,5]. Fat malabsorption therefore increases the
risk of growth failure and malnutrition with growth failure being
prevalent in children with biliary atresia, particularly in infancy [6].
For example, in a study of 755 children with biliary atresia awaiting
liver transplant more than 40% had growth failure [7]. Poor growth in
infants with cholestatic liver disease has been shown to be associ-
ated with an increased need for liver transplant [6] and mortality [7].
Dietary management of children with cholestatic liver disease
involves supplementation with medium-chain triglycerides (MCT).

https://doi.org/10.1016/j.clnu.2023.09.010
0261-5614/© 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
S. Mancell, K. Manwani, A. Dhawan et al.
MCTs are comprised of fatty acids with medium chain lengths,
primarily caprylic (C8) and capric (C10) fatty acids and a very small
amount (2e4%) of caproic (C6) and lauric (C12) fatty acids [8]. Unlike
LCT, MCTs are partially water soluble. Following lipolysis of MCT,
medium-chain fatty acids can be passively absorbed without the
need for extensive emulsification and can therefore be absorbed in
the absence of bile salts [9]. Medium-chain fatty acids do not
require chylomicron formation and are transported directly to the
liver via the portal vein [10]. The aim of MCT supplementation is to
replace the energy lost due to LCT malabsorption, with the goal to
facilitate improved growth and nutritional status. This is important
as optimised nutritional status may improve outcomes before and
after liver transplant for children with liver failure [11,12]. There is
therefore considerable potential for MCT supplementation to
improve fat absorption, growth, nutritional status and clinical
outcomes in cholestatic liver disease.
Some studies have investigated the impact of MCT supplemen-
tation on fat absorption and growth using various oils and formula
milks containing a range of MCT percentages (the proportion of
total fat derived from MCT) [13e15]. First, there is limited under-
standing of the extent and quality of research evidence investi-
gating the impact of MCT on physiological and clinical outcomes in
cholestatic liver disease, secondly, there is no consensus on the
ideal MCT percentage to use. For example, clinical guidelines from
Europe and North America (ESPGHAN, NASPGHAN) recommend
30% MCT with adjustments based on growth [12], from India
recommend 30e50% MCT [16], from Mexico recommend 30e70%
MCT [17], while clinical reviews recommend 50% MCT [18], 30e70%
MCT [18,19] and up to 75% MCT [20]. All authors advised against
giving >80% MCT as they do not contain any of the essential fatty
acids (EFA), all of which are LCT, and therefore there is a potential
risk of EFA deficiency.
The aim of this scoping review was to identify the extent and
type of evidence regarding how MCT supplementation, and the
percentage of MCT, affects fat absorption, growth, nutritional status
and clinical outcomes (morbidity, mortality, transplant) in children
with cholestatic liver disease.
2. Materials and methods
The scoping review was conducted according to JBI methodol-
ogy for scoping reviews [21] and the methods were established and
published a priori in a protocol [22].
A scoping rather than systematic review was chosen as scoping
reviews provide a rigorous framework to analyse and highlight
knowledge gaps and allow for wider inclusion criteria than sys-
tematic reviews [23]. They can be used to provide an overview or
map of a broad range of evidence.
2.1. Identification of relevant studies
The search strategy aimed to identify published as well as un-
published studies and was developed with support from a Senior
Library Assistant at King's College London. A PRESS checklist was
used to ensure comprehensiveness and precision of the search
strategy [24].
Broadly speaking, the search followed four steps: 1) Search
development and optimisation, during which relevant studies were
identified through an initial search of two databases (Ovid Medical
Literature Analysis and Retrieval System Online [MEDLINE] and
Excerpta Medica Database [EMBASE]) and the titles, abstracts and
index terms of eligible studies were extracted; 2) Electronic search,
during which the optimised search terms identified in step one
were used to perform an electronic search across nine databases; 3)
Manual search, during which the abstracts from conferences from
2160
Clinical Nutrition 42 (2023) 2159e2172
five organisations were hand-searched; and 4) Citation searching,
during which backwards and forwards citation of all eligible studies
was performed using Google Scholar.
For the electronic search, nine databases were searched
including MEDLINE (Ovid); Embase (Ovid); Cumulative Index to
Nursing and Allied Health Literature (CINAHL); PubMed; Allied and
Complementary Medicine Database (AMED); Cochrane Library;
Global Health (Ovid); Scopus; and Proquest Dissertations and
Theses Global. Databases were searched from inception until 25/10/
2022. Each database was searched separately with search terms
relevant to that database. A full search strategy for one electronic
database is shown (Supplementary Table 1).
For the manual search, all abstracts presented over the previous
ten years (2013e2022) from conferences or annual research
meetings (n ¼ 35) from the following five organisations were hand
searched: British Dietetic Association (Journal of Human Nutrition
and Dietetics); British Society of Paediatric Gastroenterology Hep-
atology and Nutrition (Frontline Gastroenterology); European So-
ciety of Pediatric Gastroenterology Hepatology and Nutrition;
North American Society for Pediatric Gastroenterology, Hepatology
and Nutrition; and World Congress of Pediatric Gastroenterology
Hepatology and Nutrition (all Journal of Pediatric Gastroenterology
and Nutrition).
2.2. Study eligibility
Studies were considered that met the following criteria, based
on population, concept, context: 1) participants aged under 18
years with cholestatic liver disease (population); 2) investigated an
intervention of MCT supplementation with or without a compar-
ator (concept); 3) MCT given as a supplement added to the diet (e.g.
as an oil added to breastmilk, formula milk, food or drink) or
incorporated into formula milk, oral nutritional supplements or
enteral formulas (concept); 4) evaluated at least one of the
following outcomes: fat absorption, growth, nutritional status or
clinical outcome (e.g. morbidity, mortality, transplant) (concept); 5)
in any setting (context). Growth refers to anthropometric measures
of weight, length/height, head circumference, mid upper arm
circumference (MUAC) or triceps skinfold thickness (TSF) measured
at two or more time points [25].
Studies were included that were published from database
inception until 2023. This broad time period was chosen in order to
include all relevant studies since MCTs were first introduced clin-
ically in the 1950s [8]. There were no limits on language to ensure
inclusion of all potentially relevant studies and to reduce the risk of
language bias [26]. Google Translate, shown to be an accurate tool
for translating studies as part of systematic reviews [27], was used
to screen and extract data from non-English-language studies.
Studies were excluded if: 1) participants had a diagnosis of in-
testinal failure, a metabolic disorder or cystic fibrosis unless the
data from only children with cholestatic liver disease could be
extracted; 2) they investigated MCT administered intravenously
unless the data from only those receiving oral/enteral MCT sup-
plementation could be extracted; and 3) they were qualitative
studies, commentary, opinion pieces, editorials, reviews or narra-
tive book chapters.
2.3. Study screening
Two independent reviewers performed screening and data
extraction with disagreements resolved through discussion and
where consensus could not occur, arbitration with a third reviewer
(KW). All identified citations were uploaded into Covidence sys-
tematic review software (Veritas Health Innovation, Melbourne,
Australia) and duplicates were automatically removed. A pilot test
S. Mancell, K. Manwani, A. Dhawan et al.
of the screening was carried out independently by both reviewers
on 25 titles/abstracts. Following comparison and discussion be-
tween the two reviewers and when >75% agreement on eligibility
of these 25 titles/abstracts was achieved, screening of the remain-
ing titles/abstracts continued independently by both reviewers for
assessment against the inclusion criteria [21]. Those that were
potentially eligible were retrieved in full text and screened against
the eligibility criteria.
2.4. Data extraction, analysis and presentation
The same two independent reviewers extracted data from
eligible studies using a pre-defined data extraction form that was
pilot tested on two studies to ensure consistency and was contin-
ually updated in an iterative process [28]. The data extracted
included details regarding the participants, concept, context,
methods and key findings relevant to the review question. Where
required, authors of studies were contacted to request missing or
additional data. The extracted data are presented as a narrative
summary and in figures or tabular form with frequency counts and
percentages related to study characteristics to summarise the
publication features, research outcomes and brief findings of the
studies [29]. For the purposes of this study, MCT percentages were
classified as low (<40% of total fat from MCT), medium (40e60%),
high (60e80%) and very high (>80%).
3. Results
3.1. Study inclusion
Following electronic database searching, 1680 studies were
identified, 481 duplicates were removed and title and abstract
screening was carried out on 1199 studies. There were 1163 ineli-
gible studies and 36 potentially eligible studies. Manual searching
of all conferences and annual research meetings from the previous
ten years (n ¼ 35) identified two studies, both of which had already
been identified through electronic database searching. Forward
citation searching and backward reference searching identified a
further four studies, three of which were potentially eligible. Full
text review was carried out on 40 studies and 24 studies met the
inclusion criteria and were included in the scoping review (Fig. 1).
3.2. Characteristics of included studies
Of the 24 included studies, there were three RCTs, one non-
randomised controlled trial, seven uncontrolled trials, eight case
series and five case reports (of which, three were individually
extracted from case series) (Table 1).
As shown in Fig. 2a, the majority of studies (n ¼ 13) were
observational (five case reports and eight case series) (shown in
blue) while there were 11 intervention studies (seven uncontrolled
trials, one non-randomised controlled trial and three RCTs) (shown
in red). Seventeen were full papers and seven were conference
abstracts only. Seventeen (70.8%) studies were published between
1964 and 1993 (Fig. 3). Of only seven studies published in the last
30 years, six were conference abstracts only and the other was a
case report.
Study locations included United Kingdom (n ¼ 7), United States
(n ¼ 7), Japan (n ¼ 3), Australia (n ¼ 2), Canada (n ¼ 2), France,
Netherlands, Poland and Switzerland (n ¼ 1 each). There were
three non-English language studies published in French [41],
German [33] and Polish [49]. The summarised characteristics of
included studies are shown in Supplementary Table 2.
2161
Clinical Nutrition 42 (2023) 2159e2172
3.3. Characteristics of included participants
The summarized characteristics of participants are shown in
Supplementary Table 2. There were 315 participants (50.2% female)
on MCT in the included studies, (this includes children receiving
MCT only and excludes those in control groups or who were not on
MCT). There were 213 (90.3%) children aged under one year and the
most common diagnoses were biliary atresia (81.5%) followed by
idiopathic cholestasis (7%) (see Supplementary Table 2). There was
no information provided relating to sex for 72 (22.9%) children,
diagnosis for 28 (8.9%) and age for 89 (28.3%) children on MCT in
the included studies. As shown in Fig. 2b, there were a total of 19
children (6%) on MCT in the three RCTs [30e32]. The remaining
studies included between one and 30 children except for two large
case series with 88 children [44] and 40 children [43] on MCT.
3.4. Characteristics of MCT supplementation
The type of supplementation included MCT formula milk only in
19 (79.2%) studies, MCT oil or emulsion only in one (4.2%) and a
combination of formula milk and oil or emulsion in four (16.7%).
The MCT percentages ranged from 21% to 100% (Supplementary
Table 3). For five studies the percentage of MCT was not reported,
only the product name, and therefore the percentage was assumed
to be the same as reported by studies published around the same
time that did report both the name and MCT percentage
[14,30,37,50] or where there were no other studies it was assumed
to be the same as the currently available product of the same name
[39]. The MCT percentages investigated in the studies are shown in
Fig. 4. Information about MCT intake, rather than just percentage
supplementation, was provided in four (16.7%) studies as MCT g/kg
[15,39] or g/day [15,33,36] but was not provided in other studies.
Information about the duration of MCT supplementation was pro-
vided in 20 (83.3%) studies and ranged from one day to 12 months
(Supplementary Table 2).
MCT was compared with no MCT in 13 (54.2%) studies; different
percentages of MCT were compared in five (20.8%) studies and in
six (25%) studies (five case series and one case report) that reported
growth in children on MCT there was no comparator
(Supplementary Table 2). In 21 (87.5%) studies the impact of MCT
supplementation on outcomes was one of the key aims, whereas for
three (12.5%) studies, children received MCT supplementation but
this was not the main focus of the study despite relevant outcomes
being reported.
3.5. Outcomes
The outcomes reported in included studies were absorption
(n ¼ 11), growth (n ¼ 14) and biochemical nutritional status (n ¼ 5)
(Fig. 5). Some studies reported more than one outcome. No studies
reported clinical outcomes (e.g. progression to transplant,
mortality).
3.6. Absorption
In the 11 studies reporting absorption, 10 measured fat ab-
sorption in 87 children [13e15,32,33,35e37,39,47] and one
measured calcium and magnesium absorption in 13 children [31].
All of the studies were published prior to 1994. Of those reporting
fat absorption, two reported stool fat content only (g) [13,37] while
eight reported the coefficient of fat absorption (CFA) (%) or reported
fat intake and stool fat content such that CFA could be calculated.
Only one study provided information regarding how fat intake was
measured (weighing bottles before and after formula milk feeds)
[32]. In terms of stool assessment and collection, four studies
S. Mancell, K. Manwani, A. Dhawan et al.
Fig. 1. Flow diagram of identification, screening and inclusion of studies.
reported using the oral dye markers carmine red [32,33,35] or
charcoal [37] to signal the start and end of the stool collection
period and one reported using a plastic bag in the nappy to ensure
complete stool collection [32]. In order to analyse the fat content of
stool, the methods described by van de Kamer [51] were used in
five studies [14,15,33,37,47], Jeejeehboy [52] in two [32,37] Bligh
and Dyer [53] in one [39] and Saxon [54] in one study [35] while
two studies used their own method involving petroleum ether
extraction [15,33] and in one the stool fat analysis method used was
not reported [36]. In one of the studies both the methods of van de
Kamer [51] and Jeejeebohy [52] were used and found to be equiv-
alent [37].
In the nine studies that investigated the impact of MCT versus
no MCT on fat absorption, fat absorption was greater on MCT than
on no MCT in all studies [13e15,33,35e37,39,47]. Only one study
compared fat absorption on different MCT percentages and found
that there was no difference in fat absorption when similar MCT
percentages were given (42% and 48%) [32].
Where it was possible to determine individual values of CFA,
absorption on MCT varied between 73% and 100% while absorption
on no MCT ranged from 20% to 97% [14,15,33,35,36,39]. The MCT
percentages used in the studies were 87e100% [13e15,33,47], 25.1%
[35] not stated [36] and a 50% MCT emulsion [39]. In most studies
infants received both MCT and LCT when on the MCT diet and so the
CFA relates to total fat absorbed rather than the CFA of only the MCT
or LCT. In two studies where it was possible to determine the ab-
sorption of each specific fat, the CFA for MCT was median 92.6%
(range 83.3e96.7%) and for LCT was 47.6% (30e70%) [36] and in one
child it was 94% versus 82% [47].
For the RCT that investigated the impact of MCT on calcium and
magnesium absorption in 13 children, calcium and magnesium ab-
sorption were greater on very high MCT (98%) versus low MCT (21%)
(Ca 46.9% versus 34.1%, Mg 43.6% versus 34.7% respectively) [31].
2162
Clinical Nutrition 42 (2023) 2159e2172
3.7. Growth
Growth was reported in 249 children on MCT in 14 studies.
Growth measurements included: weight (n ¼ 13), MUAC (n ¼ 5),
length (n ¼ 4) and TSF (n ¼ 3). Growth measurements were pre-
sented as z-scores in six studies [34,38,40,42e44] and weight gain
(g/kg/day, kg/month, kg) in four [13,32,41,49]. There was no growth
data provided for four studies [14,30,33,37] although they provided
qualitative statements relating to growth (e.g. MCT supplementa-
tion had “no effect on the weight of patients”) [37].
In four studies that compared growth on MCT versus no MCT,
growth was greater on MCT than on no MCT in nine children [13,14]
and there was no difference in 30 children [14,33,37]. In three
studies comparing different percentages of MCT there was no dif-
ference in growth [30,32,38] while in one study, a conference ab-
stract that included nine children, growth was greater on 30% and
70% MCT than on 50% MCT [34]. Growth was measured over
different time periods ranging from three days [32,33,37] to 12
months [38] and in two cases the timing of measurements was not
provided [14,34] (Supplementary Table 2). In the six studies that
did not include a comparator, growth in children given MCT sup-
plementation either declined over time [44,49] or improved
[40e43].
3.8. Biochemical nutritional status
In the five studies reporting biochemical nutritional status, four
measured EFA status in 10 children using triene-tetraene ratio
(n ¼ 3)30,45,50 or EFA concentrations (n ¼ 1) [46]. The other reported
serum lipid concentrations (cholesterol, palmitoleic acid and lino-
leic acid) in one child [48]. No other markers of nutritional status
(e.g. fat soluble vitamin status) were investigated. In one RCT of
only four children there was EFA deficiency on very high MCT (87%
 Table 1
Characteristics of studies investigating MCT supplementation in children with cholestatic liver disease.

Author, publication Participants Design Method MCT type (MCT as % Comparator Outcomes Key findings
year, country (number, sex, of total fat)
diagnosis, age)

Kaufman et al., 4 children (2F) with RCT The impact of MCT MCT formula milks: Different MCT EFA status (triene- EFA deficiency on
1992 [30] (US) alpha-1-antitrypsin percentage on EFA Pregestimil (55%) percentages tetraene ratio) very high but not
deficiency (n ¼ 2), status Portagen (87%) Growth (TSF, medium MCT
biliary atresia 55% MCT given for "2 MUAC) (n ¼ 2). No
(n ¼ 1), Alagille months and then Measured at the deficiency on either
syndrome (n ¼ 1) infants randomised to end of each month % (n ¼ 2)
Age 2.5e13 months very high (87%) or No difference in
S. Mancell, K. Manwani, A. Dhawan et al.

medium (55%) MCT for growth on the

one month followed by formulas (although
crossover to the other no numerical data
formula for 1 month. reported).
Participants were
blinded to treatment.
Kobayashi et al., 13 children with RCT The impact of MCT MCT formula milks: Different MCT Ca and Mg Ca and Mg
1974 [31] (Japan) biliary atresia percentage on calcium Crown Dia-G (21%) percentages absorption (% absorption greater
Sex not reported and magnesium Lipomeal (98%) absorption) over 3 on very high MCT
Age <15 months absorption to 4-day period versus low MCT.
(no data reported) Random assignment to Ca 46.9% (32.3
groups: e60.6) v 34.1%
Low MCT (21%) (n ¼ 10) (20.4e45.2)
Low MCT (21%) with Mg 43.6% (29.7
oral vitamin D (n ¼ 4) e55.7) v 34.7% (5.4
Low MCT (21%) with IV e46.7).
vitamin D (n ¼ 5)
Very high MCT (98%)

2163
(n ¼ 4)
In some, 2 or 3 studies
carried out.
Measurements
performed after 5d.
Lifschitz et al., 1986 2 children (F) with RCT The impact of MCT MCT formula milks: Different MCT Fat absorption No difference in fat
[32] (US) biliary atresia percentage on fat Pregestimil (42%) percentages (Stool fat, % absorption
Age 5m and 11.9m absorption and growth. Alfare (48%) absorption) over 3 between formulas
Infants given medium days No significant
MCT (48% or 42%) for 4 Growth (weight difference in
days and then gain g/kg/day) growth on formulas
absorption measured (0.3 versus 0.3 g/kg/
over 3 days followed by day and 0.7 versus
crossover to the other 0.4 g/kg/day).
formula for the same
period. The order the
milks were given in was
randomised.
Kuhni 1968 [33] 2 children with Non-randomised The use of MCT in MCT oil and No MCT (Normal Fat absorption Fat absorption
(Switzerland) biliary atresia controlled trial children with formula milk: diet) (Intake, stool fat, % greater on MCT
Sex not reported steatorrhoea due to Un-named (97%) absorption) versus no MCT
Age 2m and 4.5m different causes, measured for 3- (83.1% versus 42.7%
including in 2 children days twice in each and 79.9% versus
with biliary atresia. 6-day period. 23.3%).
Very high (97%) MCT Growth (weight) No difference in
given for 6 days daily growth (although
followed by crossover no numerical data
to no MCT for 6 days. reported).
(continued on next page)
Clinical Nutrition 42 (2023) 2159e2172
 Table 1 (continued )

Author, publication Participants Design Method MCT type (MCT as % Comparator Outcomes Key findings
year, country (number, sex, of total fat)
diagnosis, age)

The order in which this

was done was
alternated.
Beath et al., 1996 10 children Uncontrolled trial The impact of MCT MCT formula milk: Different MCT Growth (weight, Growth on 30% and
[34] (UK) Sex, diagnosis, age percentage on Un-named (30%, percentages length, TSF, MUAC 70% MCT was better
(abstract only) not reported duodenal bile salt 50%, 70%) z-score change) than 50% MCT.
concentrations, fat measured over Weight:
solubilisation and unspecified time. 30% ¼ 0.4(0.5),
S. Mancell, K. Manwani, A. Dhawan et al.

growth 50% ¼ 0.02 (0.3),

Infants given low (30%), 70% ¼ 0.2(0.3)
medium (50%) and high Length: 30% ¼ -0.06
(70%) MCT for an (0.7), 50% ¼ -
unspecified time. Group 1.3(0.8), 70% ¼ -
allocation details not 1.3(0.7)
reported. TSF: 30% ¼ 0.5 (0.8),
50% ¼ #0.2(0.5),
70% ¼ 0.6(0.7)
MUAC:
30% ¼ 0.49(0.6),
50% ¼ -0.14(0.7),
70% ¼ 0.4 (0.5)
Kobayashi et al., 7 children with Uncontrolled trial The impact of MCT formula milk: No MCT (FA milk) Fat absorption (% Mean (SD) fat
1983 [35] (Japan) biliary atresia unrepaired versus Formula No. 721 absorption) absorption was
Sex, age not repaired biliary atresia (25.1%) measured for 3e5 greater on MCT
reported on fat absorption and days (infants) or 1 than no MCT (90%
the impact of MCT on e3 days (children). (9.5) versus 84%

2164
fat absorption in 7 (11)). Greater
infants with repaired improvement in fat
biliary atresia. absorption on MCT
No MCT for "5 days and for those with
then low (25.1%) MCT jaundice versus
given. No report of how those without.
long MCT given before
measurement.
Burke and 11 children with Uncontrolled trial MCT use reviewed in MCT formula milk No MCT (Normal Fat absorption Stool fat mean (SD)
Anderson 1967 neonatal hepatitis children with Un-named (95%) diet) (Stool fat) over 3- 22g (8.8) on no MCT
[13] (Australia) (n ¼ 6), biliary malabsorption from day period v. 4g (1.8) MCT.
atresia (n ¼ 5) various causes Growth (weight Weight increased
Sex, age not including in 8 children gain/kg/month) on MCT: case
reported with liver disease. 1 ¼ 0.7, 1.1 no MCT
Fat absorption reported v. 1.5 MCT; Case
in 8 children given very 2 ¼ 1, 0.25 no MCT
high (95%) MCT for 3 v. 1.1, 0.7 MCT;
days followed by Case 3 ¼ 0.2 no
crossover to no MCT for MCT v. 1.0, 0.9, 0.5
3days. MCT
Growth reported in 3
children on alternate
months on very high
(95%) MCT/no MCT for 3
e5m.
Burke and Dank 18 children Uncontrolled trial The impact of MCT MCT oil and No MCT (Normal Fat absorption (Fat Mean (SD) stool fat
1966 [36] Sex, diagnosis, age versus no MCT on fat formula milk: diet) intake, stool fat) 14.2g (9.1) no MCT
(Australia) not reported absorption Un-named (95%) over 3-day period versus 3.3g (2.0)
Very high (95%) MCT MCT.
Clinical Nutrition 42 (2023) 2159e2172
 given for 3 days Mean (SD) fat
followed by crossover absorption 88.9%
to no MCT for 3 days (6.7) MCT and
45.4% (12.7) no
MCT.
Cohen and Gartner 11 children with Uncontrolled trial The use of MCT in the MCT formula milk: No MCT (Cow's Fat absorption (% Fat absorption
1971 [14] (US) biliary atresia management of biliary Portagen (95%) milk) absorption) over 3- mean (SD) 82% (5.7)
Sex, age not atresia day period MCT and 60% (15.7)
reported No MCT given for 3 days Growth (weight, no MCT.
and then crossover to length) at each No change in
very high (95%) MCT visit, admission growth (group 1)
for: improved growth
on MCT (group 2,
S. Mancell, K. Manwani, A. Dhawan et al.

4e23 weeks (n ¼ 5)
11e29m (n ¼ 3) 3). (No data
6e12 months (n ¼ 3) reported).
Leyland et al., 1969 3 children (2M) Uncontrolled trial The use of MCT in MCT formula milk: No MCT (Normal Fat absorption (fat Mean (SD) fat
[15] (UK) with unknown children with Portagen (95%) diet) intake, stool fat) absorption greater
cause (n ¼ 2), malabsorption due to MCT oil: measured for 3 to on MCT versus no
biliary atresia different causes Unnamed (98%) 5-day period MCT (93.6% (2.2)
(n ¼ 1) including in 3 with liver versus 59.5% (3.4)).
Age 9me15.5 y disease.
Very high (95% or 98%)
MCT given for "1 week
before fat absorption
measured followed by
crossover to no MCT.
Weber and Roy 23 children (13M) Uncontrolled trial Malabsorption and the MCT formula milk: No MCT (Normal Fat absorption Stool fat 10.9g (7
1972 [37] with biliary atresia impact of a low-fat diet Portagen (95%) diet) (stool fat) e14) on no MCT
(Canada) (n ¼ 14), paucity of supplemented with MCT oil: Growth (weight) versus 6.5g (2e8)
intrahepatic bile MCT in children with Un-named (100%) measured over a 3- MCT and for

2165
ducts (n ¼ 4), post- liver disease. day period decompensated
hepatic cirrhosis No MCT given for 3- liver disease (21.4g
(n ¼ 5) days followed by (19e32g) versus 6g
Age median 15m crossover to very high (2e9.5g).
(range 1.5m (95%) MCT for 3 days. No change in
e16.5y) MCT supplementation growth (although
was MCT formula milk no numerical data
and oil plus skimmed reported)
milk added to low fat
foods.
Martincevic et al., 24 children (15F) Case series To evaluate growth MCT formula milks: Different MCT Growth (weight, No difference in
2019 [38] with biliary atresia. following KPE before Enfamil Enfacare percentages length, MUAC, TSF growth for those
(Canada) Pre-change ¼ 17 and after change of (30%) z-scores) at first 2 given medium MCT
(abstract only) (10F) median age nutrition protocol Pregestimil (55%) visits post-KPE and before the protocol
70 d (25e90) Medium (55%) MCT at 6, 12 months. was changed and
Post-change ¼ 7 given before the change those given low
(5F) age 58 d (20 in protocol and low MCT after the
e111d) (30%) MCT given after change.
the change
Beath et al., 1993 9 children (5F) with Case series Absorption of MCT emulsion: LCT Fat absorption (fat MCT absorption
[39] (UK) biliary atresia individual fatty acids of Liquigen (50%) intake, was 98e100% and
(abstract only) (n ¼ 6), neonatal MCT and LCT % absorption) over LCT absorption was
hepatitis (n ¼ 2), MCT given alongside 3 days 36e82%.
Alagille (n ¼ 1) LCT for 3 days
Age <2 y
Bruggink et al., 30 children (22F) Case series Growth and nutritional MCT formula milk: No comparator Growth (weight, Growth increased
2018 [40] with biliary atresia status following KPE. Heparon MUAC z-scores) from baseline to 8
(Netherlands) Mean age 61 d Infants given medium Junior(49%) measured at 1, 4, 8 weeks
(abstract only) weeks post KPE Weight
(continued on next page)
Clinical Nutrition 42 (2023) 2159e2172
 Table 1 (continued )

Author, publication Participants Design Method MCT type (MCT as % Comparator Outcomes Key findings
year, country (number, sex, of total fat)
diagnosis, age)

(49%) MCT following approximately #0.6

KPE to 0 MUAC
approximately #1.8
to #1.1
Gaudier et al., 1974 4 children (2F) with Case series MCT use reviewed in MCT formula milks: No comparator Growth (weight) All patients gained
[41] (France) biliary atresia children with Portagen (95%) over 5e14 months weight (1e5 kg)
Age 1e4 m malabsorption from Triceryl (95%) over 5e14 months.
various causes (No baseline data
S. Mancell, K. Manwani, A. Dhawan et al.

including 4 children reported).

with biliary atresia.
Very high (95%) MCT
given for 5e14 months
Houchin et al., 2010 7 children (4F) with Case series The safety and efficacy MCT formula milk: No comparator Growth (weight, Median z scores
[42] (UK) biliary atresia of the MCT formula Heparon Junior length, MUAC z- increased on MCT
(abstract only) (n ¼ 4), idiopathic investigated. (49%) score change) at 4, from baseline to
(n ¼ 2), alpha-1- Medium (49%) MCT 12 w (n ¼ 7), 24 w final measurement:
antitrypsin given for up to 24 (n ¼ 3) weight change 1.09
deficiency (n ¼ 1) weeks as "60% of (0.53e1.62); length
Median age 9 w (5 energy intake change 0.47 (0.15
e28) e4.55); MUAC
change 1.10
(#0.01-3.0).
Kamat et al., 2010 40 children (27M) Case series The use of MCT MCT formula milks: No comparator Growth (weight z- Median weight at:
[43] (UK) with biliary atresia formulas and Generaid Plus (32%) score) measured on Baseline #2.27
(abstract only) (n ¼ 18), idiopathic nutritional Pregestimil (55%) starting and (#4.51- - 0.13)
management of Caprilon (75%) stopping/changing Stopping MCT-2

2166
(n ¼ 18), alpha-1-
antitrypsin cholestatic infants MCT (#4.34 to þ1.7)
deficiency (n ¼ 2), reviewed Changing to 32%
PFIC (n ¼ 1), High (75%) or medium MCT -2.04 (#0.38
Alagille (n ¼ 1); (55%) MCT given until to #4.34).
Median age 8 w (3 jaundice resolved at
e25) median 13 w (2e50)
(n ¼ 31) or until
changed to low (32%)
MCT (n ¼ 9) after 30 w
(27e47).
Kamat et al., 2016 88 children (45M) Case series The use of MCT in MCT formula milks: No comparator Growth (weight z- Mean weight z-
[44] (UK) with biliary atresia infants with biliary Generaid Plus (32%) score) measured at score dropped from
(abstract only) Median age 7.4 w atresia. Heparon Junior baseline and 6 birth until 6 weeks
(2.3e40.4) at time MCT given at different (49%) weeks. post KPE (#0.45
of KPE percentages following Pepti-Junior (50%) to #1.5).
KPE for 6 weeks. Pregestimil (55%)
Caprilon (75%)
Pettei et al., 1991 4 children (2F) with Case series The impact of MCT MCT formula milk: No MCT (Soybean EFA status (triene- There was EFA
[45] (US) Biliary atresia versus no MCT on EFA Portagen (87%) oil, cow's milk) tetraene ratio) deficiency in all
(n ¼ 3), neonatal status measured on MCT patients which
cholestasis (n ¼ 1) Very high (87%) MCT and no MCT. Details resolved after
Age 2.5e16 m given for unspecified of timing not stopping MCT.
period followed by no provided.
MCT for: 18 weeks
(n ¼ 1), unspecified
period after transplant
(n ¼ 2), 6 weeks (n ¼ 1)
Hirono et al., 1977 1 child (M) with Case report from Parenteral nutrition or MCT formula milk: No MCT (Cow's EFA status (serum Levels of
[46] (Japan) neonatal hepatitis case series MCT given and EFA Un-named (100%) milk formula) EFA arachidonic and
Clinical Nutrition 42 (2023) 2159e2172
 Age 3m status examined in concentrations) linoleic acid were
Healthy controls children with after 3 weeks lower than controls
(n ¼ 4) Age 5e11m malabsorption from while 5,8,11-
Sex not reported various causes eicosatrienoic acid
including in one with was higher,
liver disease on MCT. indicating EFA
Very high (100%) MCT deficiency
given for 3 weeks.
Healthy controls given
no MCT.
Holt et al., 1965 1 child (F) with Case report from The use of MCT was MCT formula milk: No MCT (Formula Fat absorption (% Fat absorption was
[47] (US) biliary atresia case series reported in patients Un-named (100%) milk, un-named) absorption) over a 94% on MCT, 82% on
Age 2.5 y with malabsorption 4-day period no MCT.
S. Mancell, K. Manwani, A. Dhawan et al.

due to various causes

including in one child
with biliary atresia.
Very high (100%) MCT
given for "3 days
followed by no MCT
and then very high
(100%) MCT again.
Tamir et al., 1969 1 child (M) with Case report from The impact of MCT on MCT formula milk: No MCT (Pre-MCT Serum lipid Cholesterol,
[48] (UK) unknown cause case series serum and adipose Un-named (91%) diet) concentrations palmitoleic acid
Age 2 years tissue lipids in 13 (cholesterol, and linoleic acid
children with palmitoleic acid concentrations
malabsorption from and linoleic acid) were lower on MCT
different causes, compared to no
including one with liver MCT.
disease.
No MCT given for 1

2167
week followed by very
high (91%) MCT for 3
weeks.
Jankowska et al., 1 child (M) with Case report The nutritional MCT formula milk: No comparator Growth (weight) Poor growth on
2008 [49] biliary atresia management was Un-named (70%) MCT. Weight was
(Poland) Age 18 m at reported of a child with 4.2 kg at 3 weeks,
transplant biliary atresia 6.4 kg at 9 months,
transplanted at 18 7.3 kg at 1 year.
months of age.
High (70%) MCT given
from 3 weeks until
transplant
Levy et al., 1990 1 child (M) with Case report To report on a child MCT formula milk: LCT (Microlipid) EFA status (triene- There was EFA
[50] (US) Alagille syndrome with EFA deficiency on Portagen (87%) tetraene ratio) deficiency on MCT
Age 3 y MCT. which resolved
Healthy controls EFA measured on very when LCT was
(n ¼ 44) high (87%) MCT and given
Mean age 13.1y then after an
(3.1) Sex not unspecified period on
reported an LCT supplement.
Information not
provided on whether
the MCT formula milk
continued during LCT
supplementation. EFA
compared to controls.

KPE: kasai portoenterostomy, PFIC: progressive familial intrahepatic cholestasis; CHB: conjugated hyperbilirubinaemia; EFA Essential fatty acid; *Data only available for one participant in the case series.
Clinical Nutrition 42 (2023) 2159e2172
S. Mancell, K. Manwani, A. Dhawan et al. Clinical Nutrition 42 (2023) 2159e2172

Fig. 2. Published research studies on MCT in cholestatic liver disease.

Of the 24 included studies data represent (a) the number of studies with each study design (b) the number of participants in each type of study design (data are for the number of
children receiving MCT only, excluding those not on MCT/in the control group). Observational studies (case reports and case series) are shown in shades of blue and intervention
studies (trials with or without control groups) are shown in shades of red. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web
version of this article.)

Fig. 3. Year of publication of studies on MCT in cholestatic liver disease.

Data represent the year of publication of studies. Observational studies (case reports and case series) are shown in blue and intervention studies (trials with or without control
groups) are shown in red. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

MCT) but not medium MCT (55%) for two children but no difference
for the other two children [30]. In two studies there was EFA
deficiency on very high MCT (87%) which resolved on no MCT [45]
or when an LCT supplement was given [50] and in another study a
child had EFA deficiency after having 100% MCT [46]. In two of the
studies EFA status was measured after three weeks [46] or four
weeks [30] of MCT supplementation, while in the other two studies
the duration was not specified [45,50]. In the case report that
investigated the impact of three weeks of MCT supplementation on
serum lipids, the concentrations of cholesterol, palmitoleic acid and
linoleic acid were lower on MCT compared to no MCT [48].
2168
4. Discussion
The findings of this scoping review on MCT supplementation in
children with cholestatic liver disease indicate that most of the
evidence is from small studies published over 30 years ago, with
almost a third of the studies published as conference abstracts only.
The studies used formula milks with MCT ranging from 21% to 100%
to investigate the impact of MCT supplementation on absorption,
growth and nutritional status, but no studies investigated the
impact of MCT on clinical outcomes such as progression to trans-
plant, morbidity or mortality. The findings indicate improved fat
S. Mancell, K. Manwani, A. Dhawan et al.
Fig. 4. MCT percentages in formula milks used in the 24 studies of MCT supplementation in children with cholestatic liver disease.
Data represent the MCT percentages of products used in the included studies. Percentages are grouped by colour: green ¼ low MCT (<40%), blue ¼ medium MCT (40e59%);
purple ¼ high MCT (60e80%); red ¼ very high MCT (>80%). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this
article.)
absorption on MCT compared to no MCT, no impact of MCT on
growth in most studies and higher prevalence of EFA deficiency
during very high MCT supplementation. However, most of the ev-
idence is observational and where a trial was conducted the studies
were very small with the three RCTs including between only four
and 13 participants. Some studies did not include a comparator,
particularly those that reported growth and many did not present
full data. All of these factors make it extremely difficult to make
conclusions that are rigorous enough to inform practice or be
included in clinical guidelines.
In some of the studies there was limited information regarding
the MCT supplementation with most studies stating MCT per-
centages but few providing information regarding actual MCT
intake. This is mirrored in the literature with expert opinion re-
views frequently making reference to MCT percentage rather than
intake [12,18e20]. Where MCT percentage alone is presented it is
potentially difficult to make comparisons and draw conclusions
about outcomes as differences in formula milk volume, prescription
or consumption or total fat content in addition to the MCT per-
centage would impact total MCT intake. Reporting both MCT sup-
plementation (% of total fat) and MCT intake (g/d or g/kg/d) avoids
this issue. Another challenge was that some studies did not report
MCT product names or MCT percentages were either missing or
different to current formulations.
The studies that reported fat absorption showed that fat ab-
sorption on MCT was much higher than on no MCT, but only one
study investigated absorption on different percentages. The CFA on
no MCT was in most cases well below that expected in healthy
subjects (90e95%) [55]. The CFA on MCT, although improved,
indicated ongoing fat malabsorption in some cases. This might be
because in all but two studies, that gave 100% MCT [33,47], children
were given some LCT alongside MCT and therefore may have
continued to malabsorb LCT. In the two studies where information
2169
Clinical Nutrition 42 (2023) 2159e2172
was provided, the CFA specifically of MCT absorption (as a pro-
portion of total MCT) was much greater than LCT [36,47].
In the studies that investigated fat absorption, most used the
three-day fat balance method (fat intake e fat excretion ¼ fat ab-
sorption) [56] and is considered the gold standard for measuring
CFA [57] ideally using oral dye markers to signify the start and end of
the stool collection period [56]. Despite the use of this gold-standard
method, only one study described methods for measuring fat intake
(weighing feeding bottles) and four reported using dye markers. A
challenge in infant stool collection is ensuring all stool is collected
from the nappy, which can be difficult when there are frequent
semisolid or liquid stools, as in children with cholestatic liver disease
[39] and only one study used methods to overcome this [32].
Many of the studies used an alternative or modified van de
Kamer [51] method due to concerns that the original method
incompletely extracts MCT from stool due to its water solubility
[15]. Modifying extraction methods to account for this increases
MCT extraction from 6 to 60% up to 100% [33]. The concern is that
studies using the original van de Kamer method alone may fail to
fully extract MCT from stool, thus incorrectly appearing to suggest
improved absorption.
Only one study investigated the impact of MCT on micronutrient
absorption, reporting moderately higher absorption of calcium and
magnesium absorption on very high MCT (98%) versus low MCT
(21%) [31], a finding similar to that reported in premature infants
without cholestastic liver disease [58,59] but in contrast to adults
with fat malabsorption secondary to intestinal resection [60]. The
premise is that in the presence of steatorrhoea, unabsorbed fatty
acids may bind calcium and magnesium in the intestinal lumen to
form insoluble soap complexes [12,60]. Thus, replacing LCT with
MCT could potentially reduce luminal fatty acids, resulting in
improved calcium and magnesium absorption. This is important in
cholestasis where malabsorption of calcium and magnesium
S. Mancell, K. Manwani, A. Dhawan et al.
Fig. 5. Outcomes reported in 24 studies of MCT supplementation in children with cholestatic liver disease.
The outcomes reported in the included studies are grouped by categories including: growth, absorption and biochemical nutritional status. MUAC ¼ mid-upper arm circumference;
TSF ¼ triceps skinfold thickness; EFA ¼ essential fatty acids.
further risks bone health in a group of children who are already at
risk of metabolic bone disease [12].
MCT supplementation was associated with improved growth in
just nine children from two studies [13,14] and in the other eight
studies there was no difference irrespective of the presence or
absence or percentage of MCT. This is surprising given the data on
improved fat absorption described earlier and may in some cases be
due to inadequate duration between measurements to assess
growth change, for example, in three studies weight change was
measured over just three days [32,33,37]. It is difficult to interpret
and synthesise studies due to variations in the measurements used
to assess growth and the lack of data presented in many studies.
Only six studies presented z-scores, all published in the last 30
years, which enables comparison between ages and sex and is
recommended by the World Health Organisation [25].
High MCT supplementation was associated with EFA deficiency,
although there were few studies including few children. The
triene-tetraene ratio or triene levels were regularly reported
although this measure may not be suitable in cholestasis [61,62].
The risk of EFA deficiency may relate to low intake of EFA from
MCT formula milks and fat malabsorption [30] rather than due to
MCT supplementation per se. For example, previous studies re-
ported that children with cholestasis not receiving MCT supple-
mentation had significantly depleted plasma EFA compared to
controls [62,63]. The recommendation is to supplement with EFA
during MCT supplementation [45] providing 3% energy from
2170
Clinical Nutrition 42 (2023) 2159e2172
linoleic acid and 0.7e1% from alpha-linolenic acid to prevent EFA
deficiency [12].
There were no other measures of nutritional status investigated
in relation to MCT supplementation, for example fat-soluble
vitamin status. Fat soluble vitamin deficiency is common in chil-
dren with cholestatic liver disease [64,65] particularly vitamins D
and E at first presentation [66]. As MCT is not a source of fat-soluble
vitamins, the impact of MCT supplementation and its percentage on
FSV status could be an important area of investigation.
4.1. Strengths and limitations
The strength of this scoping review is that it is the first to
comprehensively review the evidence for the use of MCT supple-
mentation in children with cholestatic liver disease. The wide time
period studied, comprehensive search strategy and the inclusion of
non-English language studies helped to ensure all relevant studies
were captured. The major limitation relates to the publication date
of the studies. Many studies had missing or insufficient data and
because they were published "30 years ago it was not possible to
contact the authors for clarification, as this predated widespread
availability of email addresses. This made it difficult to assess the
evidence in some cases where the methods were unclear or where
information (e.g. % MCT), was not provided. Assumptions about the
MCT percentages used in studies published so long ago may have
been incorrect.
S. Mancell, K. Manwani, A. Dhawan et al.
5. Conclusion
In conclusion, the limited, mostly observational evidence from
more than 30 years ago points to greater fat absorption on MCT
compared to no MCT and EFA deficiency on high MCT in children
with cholestatic liver disease. High quality RCTs are required,
particularly examining the impact of MCT at different percentages
(including 0%) on growth, nutritional status and outcomes. Future
studies should ideally additionally report MCT intake to enable
comparison with the literature.
Funding statement
Sara Mancell, Clinical Doctoral Research Fellow (NIHR302152), is
funded by Health Education England (HEE)/National Institute for
Health Research (NIHR) for this research. The views expressed in
this publication are those of the author(s) and not necessarily those
of the NIHR, National Health Service or the UK Department of
Health and Social Care.
Author contribution
Sara Mancell: Conceptualization, Methodology, Formal Analysis,
Investigation, Writing- Original draft, Funding acquisition. Kar-
ishma Manwani: Investigation, Writing-review and editing. Anil
Dhawan: Conceptualization, Writing-review and editing, Funding
acquisition. Kevin Whelan: Conceptualization, Methodology,
Writing-review and editing, Supervision, Funding acquisition.
Conflict of interest
There are no conflicts of interest in this project.
Acknowledgement
We would like to acknowledge the Library Assistants at King's
College London for their support with developing the search
strategy.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.clnu.2023.09.010.
References
[1] Tessitore M, Sorrentino E, Sciano Di Cola G, Colucci A, Vajro P, Mandato C.
Malnutrition in pediatric chronic cholestatic disease: an up-to-date overview.
Nutrients 2021;13:1e23.
[2] Fawaz R, Baumann U, Ekong U, Fischler B, Hadzic N, Mack CL, et al. Guideline
for the evaluation of cholestatic jaundice in infants: joint recommendations of
the North American society for pediatric gastroenterology hepatology and
nutrition and the European society for pediatric gastroenterology hepatology
and nutrition. JPGN 2017;64:154e68.
[3] Perretta L, Ouldibbat L, Hagadorn JI, Brumberg HL. High versus low medium
chain triglyceride content of formula for promoting short-term growth of
preterm infants. Cochrane Database Syst Rev 2021;23(2):CD0027777.
[4] Department of Health. Dietary reference values: a guide. London: HMSO;
1991.
[5] EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific
opinion on dietary reference values for fats, including saturated fatty acids,
polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids and
cholesterol. EFSA J 2010;8(3):1461.
[6] DeRusso PA, Ye W, Shepherd R, Haber BA, Shneider BL, Whitington PF, et al.
Growth failure and outcomes in infants with biliary atresia: a report from the
biliary atresia research consortium. Hepatology 2007;46(5):1632e8.
[7] Utterson EC, Shepherd RW, Sokol RJ. Biliary atresia: clinical profiles, risk
factors and outcomes of 755 patients listed for liver transplantation. J Pediatr
2005;147:180e5.
2171
Clinical Nutrition 42 (2023) 2159e2172
[8] Traul KA, Driedger A, Ingle DL, Nakhasi D. Review of the toxicologic properties
of medium-chain triglycerides. Food Chem Toxicol 2000;38:79e98.
[9] Schonfeld P, Wojtczak L. Short- and medium-chain fatty acids in energy
metabolism: the cellular perspective. J Lipid Res 2016;57:943e54.
[10] Marten B, Pfeuffer M, Schrezenmeir J. Medium-chain triglcyerides. Int Dairy J
2006;16:1374e82.
[11] Shepherd RW, Chin SE, Cleghorn GJ, Patrick M, Ong TH, Lynch SV, et al.
Malnutrition in children with chronic liver disease accepted for liver trans-
plantation: clinical profile and effect on outcome. J Paediatr Child Health
1991;27:295e9.
[12] Mouzaki M, Bronsky J, Gupte G, Hojsak I, Jahnel J, Pai N, et al. Nutrition
support of children with chronic liver disease: a joint position paper of
NASPGHAN and ESPGHAN. JPGN 2019;69(4):498e511.
[13] Burke V, Anderson CM. Experience with medium chain triglycerides in mal-
absorptive states in childhood. Aust paediat J 1967;3(3):135e43.
[14] Cohen M, Gartner L. The use of medium chain triglycerides in the manage-
ment of biliary atresia. J Pediatr 1971;79(3):379e84.
[15] Leyland FC, Fosbrooke AS, Lloyd JK, Segall MM, Tamir I, Tomkins R, et al. Use of
medium-chain triglyceride diets in children with malabsorption. Arch Dis
Child 1969;44(234):170e9.
[16] Puri P, Dhiman RK, Taneja S, Tandon P, Merli M, Anand AC, et al. Nutrition in
chronic liver disease: consensus statement of the Indian national association
for the study of the liver. J Clin Exp Hepatol 2021;11(1):97e143.
[17] Flores-Calderon J, Cisneros-Garza LE, Chavez-Barrera JA, Vazquez-Frias R,
Reynoso-Zarzosa FA, Martinez-Bejarano DL, et al. Consensus on the man-
agement of complications of cirrhosis of the liver in pediatrics. Rev Gastro-
enterol Me !xico 2022;87(4):462e85.
[18] Smart K, Alex G, Hardikar W. Feeding the child with liver disease: a review
and practical feeding guide. J Gastroenterol Hepatol 2011;26:810e5.
[19] Baker A, Stevenson R, Dhawan A. Guidelines for nutritional care for infants
with cholestatic liver disease before liver transplantation. Pediatr Transplant
2007;11:825e34.
[20] Yang C, Perumpail BJ, Yoo ER, Ahmed A, Kerner Jr JA. Nutritional needs and
support for children with chronic liver disease. Nutrients 2017;9(10):1e16.
[21] Peters M.D.J., Godfrey C., McInerney P., Munn Z., Tricco A.C., Khalil H. Chapter
11: scoping reviews. In: Aromataris E., Munn Z., editors. JBI manual for evi-
dence synthesis, JBI; 2020. Available at: https://synthesismanual.jbi.global.
[Accessed 1 March 2023].
[22] Mancell S, Manwani K, Whelan K. Scoping review to evaluate the evidence for
how medium-chain triglycerides impact on fat absorption, growth, nutritional
status and clinical outcomes in children with cholestastic liver disease. OSF;
2022. https://osf.io/bdztc. [Accessed 1 March 2023]. Published Nov 18.
[23] Munn Z, Peters MDJ, Stern C, Tufanaru C, McArthur A, Aromataris E. Sys-
tematic review or scoping review? Guidance for authors when choosing be-
tween a systematic or scoping review approach. BMC Med Res Methodol
2018;18(143):1e7.
[24] McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS
peer review of electronic search strategies: 2015 guideline statement. J Clin
Epidemiol 2016;75:40e6.
[25] De Onis M, Blossner M. The World Health Organisation global database on
child growth and malnutrition: methodology and applications. Int J Epidemiol
2003;32:518e26.
[26] Pieper D, Puljak L. Language restrictions in systematic reviews should not be
imposed in the search strategy but in the eligibility criteria if necessary. J Clin
Epidemiol 2020;132:146e7.
[27] Jackson JL, Kurijama A, Anton A, Choi A, Fournier J, Geier A, et al. The accuracy
of Google Translate for abstracting data from non-English-language trials for
systematic reviews. Ann Intern Med 2019;171(9):677e9.
[28] Pollock D, Davies EL, Peters MDJ, Tricco AC, Alexander L, McInerney P, et al.
Undertaking a scoping review: a practical guide for nursing and midwifery
students, clinicians, researchers and academics. J Adv Nurs 2021;77:2102e13.
[29] Peters MDJ, Godfrey C, McInerney P, Khalil H, Larsen P, Marnie C, et al. Best
practice guidance and reporting items for the development of scoping review
protocols. JBI Evid Synth 2022;20(4):953e68.
[30] Kaufman SS, Scrivner DJ, Murray ND, Vanderhoof JA, Hart MH, Antonson DL.
Influence of Portagen and Pregestimil on essential fatty acid status in infantile
liver disease. Pediatrics 1992;89(1):151e4.
[31] Kobayashi A, Utsunomiya T, Ohbe Y, Nagashima Y. Intestinal absorption of
calcium and magnesium in hepatobiliary disease in infancy. Arch Dis Child
1974;49(2):90e6.
[32] Lifschitz CH, Gopalakrishna GS, Nichols B. Tolerance and fat absorption of a
special infant formula. Nutr Rep Int 1986;33(4):585e93.
[33] Kuhni M. [Nutrition of children with steatorrhea using fats of medium-chain
fatty acids]. Schweiz Med Wochenschr 1968;98(20):755e9.
[34] Beath S, Jonson S, Willis KD, Kelly DA, Booth IW. Growth and luminal fat
solubilisation in cholestatic infants on medium chain triglyceride (MCT). JPGN
1996;22(4):443.
[35] Kobayashi A, Utsunomiya T, Ohbe Y, Nagashima Y. Fat absorption in patients
with surgically repaired biliary atresia. Helv Paediatr Acta 1983;38(4):
307e14.
[36] Burke V, Dank D. Medium chain triglyceride diet: its use in treatment of liver
disease. BMJ 1966;2(5521):1050e1.
[37] Weber A, Roy CC. The malabsorption associated with chronic liver disease in
children. Pediatrics 1972;50(1):73e83.
S. Mancell, K. Manwani, A. Dhawan et al.
[38] Martincevic I, Haliburton B, Ng VL, Ling SC, Kamath BM. Early growth pat-
terns of infants following kasai portoenterostomy: QI update of single
center standardized nutrition protocol. JPGN 2019;68(Supplement 1):
842e3.
[39] Beath S, Johnson T, Willis K, Hooley I, Brown G, Booth I, et al. Superior ab-
sorption of medium-chain triacylglycerols compared with conventional di-
etary long-chain fats in children with chronic liver disease. Proc Nutr Soc
1993;52(3):253A.
[40] Bruggink J, Grutters LA, Verkade HJ, Hulscher JBF, De Kleine RHJ, Dijkstra T.
Nutritional care for infants with biliary atresia after kasai hepatoportoenter-
ostomy: regular or aggressive? JPGN 2018;66(Supplement 2):720e1.
[41] Gaudier B, Nuyts JP, Ryckewaert P, Giard P. [Indications for medium-chain
triglycerides in pediatrics]. Pediatrie 1974;26(6):641e54.
[42] Houchin M, Kamat D, Leibbrandt C, Hind J, Dhawan A. Safety and efficacy of
Heparon Junior in infants with cholestatic liver disease. JPGN 2010;50(Sup-
plement 7):E53.
[43] Kamat D, Houchin M, Hind J, Dhawan A. Nutritional management of infants
with cholestasis in a tertiary paediatric liver unit. JPGN 2010;50(Supplement
7):E1e2.
[44] Kamat D, Mancell S, Kyrana S, Fatima T, Mortimer H, Moolenschot K, et al. The
use of specialist medium chain triglyceride (MCT) formulas in infants with
biliary atresia. JPGN 2016;62(Supplement 1):769.
[45] Pettei MJ, Daftary S, Levine JJ. Essential fatty acid deficiency associated with
the use of a medium-chain-triglyceride infant formula in pediatric hep-
atobiliary disease. Am J Clin Nutr 1991;53(5):1217e21.
[46] Hirono H, Suzuki H, Igarashi Y, Konno T. Essential fatty acid deficiency
induced by total parenteral nutrition and by medium-chain triglyceride
feeding. Am J Clin Nutr 1977;30(1):1670e6.
[47] Holt PR, Hashim SA, Vanitallie TB. Treatment of malabsorption syndrome and
exudative enteropathy with synthetic medium chain triglycerides. Am J
Gastroenterol 1965;43:549e59.
[48] Tamir I, Gould S, Fosbrooke AS, Lloyd JK. Serum and adipose tissue lipids in
children receiving medium-chain triglyceride diets. Arch Dis Child
1969;44(234):180e6.
[49] Jankowska I, Neuhoff-Murawksa J, Socha P, Pawlowska J, Socha J. Clinical
aspects of nutrition in children with chronic cholestasis- on the basis of a
selected case. Przegla˛ d Gastroenterol 2008;3(3):139e42.
[50] Levy J, DeFelice A, Lepage G. Essential fatty acid deficiency mimicking
porphyria cutanea tarda in a patient with chronic cholestasis. JPGN
1990;10(2):242e5.
[51] van de Kamer JH, Bokkel Huinink TEN, Weyers JA. Rapid method for the
determination of fat in feces. J Biol Chem 1949;177:347e55.
2172
Clinical Nutrition 42 (2023) 2159e2172
[52] Jeejeebhoy KN, Ahmad S, Kozak G. Determination of fecal fats containing both
medium and long chain triglycerides and fatty acids. Clin Biochem 1970;3:
157e63.
[53] Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification.
Can J Biochem Physiol 1959;37(8):911e7.
[54] Saxon GJ. A method for the determination of the total fats of undried feces and
other moist masses. J Biol Chem 1914;17:99.
[55] Borowitz D, Konstan MW, O’Rourke A, Cohen M, Hendeles L, Murray FT. Co-
efficients of fat and nitrogen absorption in healthy subjects and individuals
with cystic fibrosis. J Pediatr Pharmacol Therapeut 2007;12:47e52.
[56] Borowitz D, Aronoff N, Cummings LC, Maqbool A, Mulberg AE. Coefficient of
fat absorption to measure the efficacy of pancreatic enzyme replacement
therapy in people with cystic fibrosis. Gold standard or coal standard?
Pancreas 2022;51(4):310e8.
[57] Dorsey J, Buckley D, Summer S, Jandacek RJ, Rider T, Tso P, et al. Fat malab-
sorption in cystic fibrosis: comparison of quantitative fat assay and a novel assay
using fecal lauric/behenic acid. J Pediatr Gastroenterol Nutr 2010;50(4):441e6.
[58] Sulkers EJ, Lafeber HN, Degenhart HJ, Lindemans J, Sauer PJJ. Comparison of
two pretem formulas with or without addition of medium-chain triglycerides
(MCT) II: effects on mineral balance. JPGN 1992;15:42e7.
[59] Tantibhedhyangkul P, Hashim SA. Medium-chain triglyceride feeding in pre-
mature infants: effects on calcium and magnesium absorption. Pediatrics
1978;61(4):537e45.
[60] Hadderslev KV, Jeppesen PB, Morensen PB, Saun M. Absorption of calcium and
magnesium in patients with intestinal resections treated with medium chain
fatty acids. Gut 2000;46:819e23.
[61] Pavlovski CJ. Screening for essential fatty acid deficiency in at risk infants. Med
Hypotheses 2009;73:910e6.
[62] Socha P, Koletzko B, Pawlowska J, Socha J. Essential fatty acid status in chil-
dren with cholestasis in relation to serum bilirubin concentration. J Pediatr
1997;131(5):700e6.
[63] Socha P, Koletzko B, Swiatkowska E, Pawlowska J, Stolarczyk A, Socha J.
Essential fatty acid metabolism in infants with cholestasis. Acta Paediatr
1998;87:278e83.
[64] Shneider BL, Magee JC, Bezerra JA, Haber B, Karpen SJ, Raghunathan T, et al.
Efficacy of fat-soluble vitamin supplementation in infants with biliary atresia.
Pediatrics 2012;130:e607e14.
[65] Ng J, Paul A, Wright N, Hadzic N, Davenport M. Vitamin D levels in infants with
biliary atresia: pre- and post-kasai portoenterostomy. JPGN 2016;62:746e50.
[66] Mancell S, Islam M, Dhawan A, Whelan K. Fat-soluble vitamin assessment,
deficiency and supplementation in infants with cholestasis. JHND 2021;35(2):
273e9.