ArticlePDF AvailableLiterature Review

Impact of Conjugated Linoleic Acid (CLA) on Skeletal Muscle Metabolism

Authors:

Abstract

Conjugated linoleic acid (CLA) has garnered special attention as a food bioactive compound that prevents and attenuates obesity. Although most studies on the effects of CLA on obesity have focused on the reduction of body fat, a number of studies have demonstrated that CLA also increases lean body mass and enhances physical performances. It has been suggested that these effects may be due in part to physiological changes in the skeletal muscle, such as changes in the muscle fiber type transformation, alteration of the intracellular signaling pathways in muscle metabolism, or energy metabolism. However, the mode of action for CLA in muscle metabolism is not completely understood. The purpose of this review is to summarize the current knowledge of the effects of CLA on skeletal muscle metabolism. Given that CLA not only reduces body fat, but also improves lean mass, there is great potential for the use of CLA to improve muscle metabolism, which would have a significant health impact.
Lipids
DOI 10.1007/s11745-015-4115-8
1 3
REVIEW
Impact of Conjugated Linoleic Acid (CLA) on Skeletal Muscle
Metabolism
Yoo Kim1 · Jonggun Kim2 · Kwang‑Youn Whang2 · Yeonhwa Park1
Received: 22 September 2015 / Accepted: 16 December 2015
© AOCS 2016
Abbreviations
ACC Acetyl-CoA carboxylase
AMPK AMP-activated protein kinase
BMR Basic metabolic rate
CLA Conjugated linoleic acid
CPT Carnitine palmitoyltransferase
ERR Estrogen-related receptor
FOXO Forkhead box O
GLUT4 Glucose transporter type 4
IL-6 Interleukin 6
LPL Lipoprotein lipase
MEF2 Myocyte enhancer factor 2
MHC Myosin heavy chain
NFκB Nuclear factor kappa-light-chain-enhancer of
activated B cells
NRF Nuclear respiratory factor
PGC-1α Peroxisome proliferator-activated receptor γ
coactivator 1α
PPARδ Peroxisome proliferator-activated receptor δ
RMR Resting metabolic rate
SIRT1 Silent information regulator two protein 1
TAG Triglyceride
TNF-α Tumor necrosis factor α
UCP Uncoupling protein
Introduction
The presence of conjugated linoleic acid (CLA, conjugated
octadecadienoic acid) in milk was first reported in the 1930s,
but it was not until the 1980s that CLA was shown to be a
bioactive food component [1]. CLA is formed during the
biohydrogenation of linoleic acid to stearic acid by rumen
bacteria [2]. In addition, trans-11 vaccenic acid (another
metabolite of biohydrogenation) is known to be converted
Abstract Conjugated linoleic acid (CLA) has garnered
special attention as a food bioactive compound that pre-
vents and attenuates obesity. Although most studies on the
effects of CLA on obesity have focused on the reduction
of body fat, a number of studies have demonstrated that
CLA also increases lean body mass and enhances physi-
cal performances. It has been suggested that these effects
may be due in part to physiological changes in the skeletal
muscle, such as changes in the muscle fiber type transfor-
mation, alteration of the intracellular signaling pathways
in muscle metabolism, or energy metabolism. However,
the mode of action for CLA in muscle metabolism is not
completely understood. The purpose of this review is to
summarize the current knowledge of the effects of CLA
on skeletal muscle metabolism. Given that CLA not only
reduces body fat, but also improves lean mass, there
is great potential for the use of CLA to improve mus-
cle metabolism, which would have a significant health
impact.
Keywords CLA · Conjugated linoleic acid · Skeletal
muscle metabolism · Obesity · Lean body mass · Physical
activity
This manuscript is based on work presented at the 2015 AOCS
Annual Meeting.
* Yeonhwa Park
ypark@foodsci.umass.edu
1 Department of Food Science, University of Massachusetts,
102 Holdsworth Way, Amherst, MA 01003, USA
2 Division of Biotechnology, Korea University, Seoul 136-713,
Republic of Korea
Lipids
1 3
to cis-9,trans-11 CLA by Δ9-desaturase in the tissues [3].
Thus, the primary dietary sources of CLA are meats and
dairy products from ruminants, although the overall CLA
intake from food is not considered substantial [4]. It has been
reported that CLA content ranges from 0.34 to 1.07 % of the
total fat in dairy products, and 0.12 to 0.68 % in raw or pro-
cessed beef [4]. In the United States, the average daily intake
of CLA from food sources is 104–151 mg and 176–212 mg
for women and men, respectively [5]. Accordingly, studies
have reported serum CLA levels of approximately 20 μM, or
0.1 % of total fatty acids, in subjects with low dairy or meat
consumption [6, 7], and approximately 50 to 180 μM with
CLA supplementation of 0.8–3.2 g per day for 2 months [7].
There are at least 28 known CLA isomers. Among
them, the cis-9,trans-11 and trans-10,cis-12 isomers have
been the focus of studies on various biological effects of
CLA [8]. The cis-9,trans-11 isomer is a naturally predomi-
nant isomer, accounting for over 80 % of naturally occur-
ring CLA [4]. In addition to the cis-9,trans-11 isomer, the
trans-10,cis-12 isomer is found at very low levels in nat-
ural foods, but, when CLA is produced by chemical syn-
thesis, this isomer is formed in significant amounts [810].
Currently, most commercial CLA preparations comprise
almost equal amounts of cis-9,trans-11 and trans-10,cis-12
isomers, up to >90 % of total CLA, and these preparations
are referred to as CLA mixtures or 50:50 mixtures.
CLA contains a trans configuration, and as there are
known negative health issues associated with trans fat,
some clarification with regard to CLA and trans fatty acids
is warranted. The definition of trans fat labeling by the US
Food and Drug Administration (FDA) is “all unsaturated
fatty acids that contain one or more isolated double bonds in
a trans configuration” [11]. It is clear, therefore, that CLA is
excluded from "trans" fat product labeling, as it has a trans
double bond that is conjugated, not isolated. Furthermore,
in July 2008, the US FDA approved CLA mixtures for
GRAS (generally recognized as safe) status in specific food
categories, including fluid milk, yogurt, meal-replacement
shakes, nutritional bars, fruit juices, and soy milk. Thus, it is
expected that there will be an increase in CLA in foodstuffs,
resulting in increased CLA intake for human health benefits.
CLA and Body Composition
Since 1997, with the discovery of the effects of CLA on
body composition in a mouse model [12], numerous studies
in various mammalian models have reported the effects of
CLA supplementation on the modulation of body composi-
tion by reducing body fat and/or increasing lean body mass
[810, 1316]. While most studies in CLA have focused
on the reduction of body fat, there is significant evidence
supporting a concurrent increase in lean body mass, body
proteins, or specific skeletal muscle mass [5, 8, 16, 17].
CLA was also confirmed to increase total protein content
(not only %) as a representation of lean mass in animals
[12]. Tables 1 and 2 summarize studies that have investi-
gated changes in body composition in rodents. Of the two
major isomers, the trans-10,cis-12 CLA isomer signifi-
cantly correlates with this effect [1821]. Some researchers
have suggested that CLA supplementation causes re-parti-
tioning of the body composition, with fewer adipose depots
and greater lean mass [22]. This observation was further
supported in a pig model, where a CLA mixture fed to pigs
at levels between 0.25 and 2 % of their diet acted as a re-
partitioning agent to induce a reduction in back fat and an
increase in lean body mass [2327].
To date, there have been approximately 100 human stud-
ies investigating the regulation of body fat by CLA, and
Table 3 summarizes only those in which changes in both
body fat and lean body mass were reported. Compared to
the results observed in animal models, CLA intervention
studies in humans has yielded less substantial and more
inconsistent results (Table 3). Among the clinical trials
investigating the effects of CLA on both body fat and lean
mass, five publications reported changes in both [2832],
while two studies reported increases in lean body mass
with no effect on body fat [33, 34]. Schoeller et al. [35]
performed a meta-analysis of 18 independent clinical stud-
ies assessing the effect of CLA on lean body mass, and
concluded that CLA supplementation led to a relatively
rapid onset of increased lean body mass, although the total
increase was not remarkable (less than 1 %). This conclu-
sion is further supported by a study of CLA in a mouse
model [36], in which an increase in lean muscle mass pre-
ceded a reduction in fat mass. These observations suggest
a potentially significant role of the muscle in the effects of
CLA on body composition.
Mechanism of CLA‑Mediated Change in Body
Composition
Multiple mechanisms have been suggested to explain the
effects of CLA on body composition [16, 17, 37]. These
include CLA-mediated energy modulation, including
reduced energy intake and enhanced energy expenditure,
along with the inhibition of fat accumulation in adipose
tissue.
The balance between energy intake and energy expendi-
ture is important for proper weight regulation. Energy
intake is from the food consumed, while energy expendi-
ture is the sum of the basal metabolic rate (BMR), thermo-
genesis, and physical activity. First, with regard to CLA and
energy intake, some studies have demonstrated that CLA-
fed mice ate less food, whereas other studies have reported
inconsistent results (Tables 1, 2) [3843]. However, some
Lipids
1 3
Table 1 Summary of mouse studies on conjugated linoleic acid (CLA) and body composition
References Mouse CLA supplementation ResultseMuscle metabolism
StrainaGenderbFormcDosage (%)dDuration BW BFM LBM Food intake Energy expenditurefBiomarkersg
Park et al. [12]ICR F + M Mixture 0.5 4 weeks ↓ ↑ ↓ CPT
West et al. [51]AKR/J M Mixture 1.0–1.2 6 weeks ↓ ↑ EE/ RQ
DeLany et al. [146]AKR/J M Mixture 0.25–1.0 6 weeks ↓ ↑
Park et al. [36]ICR F Mixture 0.5 8 weeks ↓ ↑ ↓
Park et al. [18]ICR F Mixture/c9t11/
t10c12
0.25–0.5 4 weeks by t10c12 ↓ ↑ ↓
Tsuboyama et al.
[65]
C57BL/6J F Mixture 1.0 5 months TNF-α/
GLUT4
Park et al. [147]ICR M Mixture 0.1 4 weeks ↓ ↑
Ohnuki et al. [53]ddY M Mixture 0.25–1.0 4 and 8 weeks Oxygen consumption
Peters et al. [73]PPARα-KO M Mixture 0.5 4 weeks ↓ ↑ CPT1/
UCP2
Park et al. [148]ICR F Mixture 0.3 2 weeks – –
Ntambi et al. [149]ICR F Mixture 1.0 4 weeks ↓ ↑
Hayman et al.
[150]
BALB/c M Mixture 0.1–2.0 4 weeks ↓ ↑ EE/VA/REROxygen
consumption
Warren et al. [151]C57BL/6N F c9t11/t10c12 0.5 8 weeks
Chardigny et al.
[152]
ICR F + M c9t11/t10c12 1.0 6 weeks ↓ ↑
Terpstra et al.
[153]
BALB/c M Mixture 0.5 6 weeks ↓ ↑ EE
Hargrave et al.
[154]
MH/ML M Mixture 0.5 8 weeks
Park et al. [155]ICR M t10c12 0.5 3 weeks ↓ ↑
Javadi et al. [156]BALB/c M Mixture 0.5 3 and 12 weeks ↓ ↑
Ohashi et al. [157]C57BL, KK,
KKAy
F Mixture 0.5 4 weeks – –
Javadi et al. [158]BALB/c M Mixture 4.0 5 weeks – – EE
Park et al. [159]ICR F Mixture 0.5 4 weeks ↓ ↑ ↓
de Roos et al. [160]ApoE KO M c9t11/t10c12 2.1 12 weeks – –
Hargrave et al.
[161]
M Mixture 0.5 2 and 8 weeks
Winzell et al. [162]C57BL/6J F Mixture 1.0 12 weeks ↓ ↑
Bhattacharya et al.
[163]
BALB/c M Mixture 0.5 14 weeks EE
Viswanadha et al.
[164]
CD-1 F t10c12 0.15/0.3 6 weeks
Lipids
1 3
Table 1 continued
References Mouse CLA supplementation ResultseMuscle metabolism
StrainaGenderbFormcDosage (%)dDuration BW BFM LBM Food intake Energy expenditurefBiomarkersg
Park et al. [44]ICR F + M Mixture 0.5 4 weeks ↓ ↑ ↓
Rahman et al.
[165]
C57BL/6J F Mixture 0.5 8 weeks – –
Javadi et al. [166]BALB/c M Mixture 0.5 4 weeks – – EE
Park et al. [16]ICR M Mixture 0.5 4 weeks ↓ ↑
Hur et al. [167]N2KO F t10c12 0.5 12 weeks
Andreoli et al.
[168]
CF-1 M Mixture 0.3 4 weeks
Halade et al. [97]C57BL/6J F Mixture/c9t11/
t10c12
0.5 6 months ↓ ↑
Moon et al. [169]ob/ob M Mixture 1.0 6 weeks ↓ ↑
Halade et al. [20]C57BL/6J F Mixture/c9t11/
t10c12
0.5 6 months ↓ ↑
Park et al. [55]129Sv/J F Mixture 0.5 4 weeks ↓ ↑ EE/ RQ CPT-1/
UCP2/
GLUT 4
Parra et al. [170]C57BL/6J M Mixture 3/10 mg/day 5 weeks – –
Halade et al. [171]C57BL/6J F Mixture/c9t11/
t10c12
0.5 6 months ↓ ↑
Park et al. [172]ICR M Mixture/c9t11/
t10c12
0.22/0.5 4 weeks ↓ ↑
Fedor et al. [173]C57BL/6N F t10c12 0.5 4 weeks
Scalerandi et al.
[174]
CF-1 M Mixture 1.0 4 weeks – –
a ApoE KO apolipoprotein E knockout; ddY Deutschland, Denken, and Yoken; MH high metabolic rate; ML low metabolic rate; N2KO nescient helix-loop-helix 2 gene knockout; PPARα-KO
peroxisome proliferator-activated receptor α knockout; SENCAR sensitive to carcinogenesis
b F female, M male
c Mixture, a mixed isomer of cis-9,trans-11 and trans-10,cis-12; c9t11, cis-9,trans-11 CLA isomer; t10c12,trans-10,cis-12 CLA isomer
d Dosage (%) denotes a designated weight percentage of CLA in diet
e BW body weight; BFM body fat mass; LBM lean body mass; no change; increase; decrease. All changes are based on significant differences between or within groups as reported in
publications
f EE energy expenditure; RER respiratory energy ratio; RQ respiratory quotient; VA voluntary activity
g CPT carnitine palmitoyltransferase, GLUT4 glucose transporter type 4, IL-6 interleukin 6, TNF-α tumor necrosis factor alpha, UCP2 uncoupling protein 2, no change
Lipids
1 3
have suggested that the temporary reduction in food intake
as seen with a CLA-containing diet may be due to its palat-
ability when CLA is used as a free fatty acid. Moreover, in
a study using a pair-feeding comparison, changes in body
composition occurring with CLA were shown to be inde-
pendent of reduced food intake [44], and human clinical
trials showed no effect of CLA supplementation on food
intake [29, 30, 4549]. These human studies all used self-
reported food intake methods, which calls into question
their validity [50]. Nevertheless, despite the lack of conclu-
sive evidence regarding the relationship between CLA and
dietary intake in humans, it is unlikely that the reduction in
food intake is the main mechanism of action for the change
in body composition seen with CLA.
Enhanced energy expenditure is one key to controlling
body composition. Several animal studies have suggested
that CLA increases overall energy expended [43, 5158].
In clinical trials, CLA supplementation was shown to
Table 2 Summary of rat studies on conjugated linoleic acid (CLA) and body composition
a F female, M male
b Mixture, a mixed isomer of cis-9,trans-11 and trans-10,cis-12; c9t11, cis-9,trans-11 CLA isomer; t10c12,trans-10,cis-12 CLA isomer
c Dosage (%) denotes a designated weight percentage of CLA in diet
d BW body weight, BFM body fat mass, LBM lean body mass; no change, increase; decrease. All changes are based on significant differ-
ences between or within groups as reported in publications
e TAG triglyceride
References Rat CLA supplementation ResultsdMuscle metabolism
Strain GenderaFormbDosage
(%)cDuration BW BFM LBM Food
intake
Energy
expendi-
ture
Biomarkerse
Stangl et al.
[22]
SD M Mixture 3.0 7 weeks ↓ ↑
Azain et al.
[175]
SD F Mixture 0.25/0.5 1, 5 and
7 weeks
– –
Sisk et al.
[176]
Zucker M Mixture 0.5 5 and
8 weeks
– –
Kim et al.
[177]
SD M Mixture 0.5-1.0 9 weeks
Yamasaki et
al. [178]
SD M Mixture 1.5 3 weeks
Henriksen et
al. [179]
Zucker F Mixture/
c9t11/
t10c12
0.42 g/day 3 weeks by Mix-
ture and
t10c12
by
t10c12
protein
carbonyl/
intra-
muscular
TAG /
glucose
uptake by
Mixture
and
t10c12
Sanders et
al. [180]
Zucker F Mixture/
c9t11/
t10c12
0.42 g/day 3 weeks by Mix-
ture and
t10c12
– –
Botelho et
al. [181]
Wistar M Mixture 2.0 6 weeks ↑ ↑
Ogborn et
al. [182]
Han:
SPRD-
cy
F + M Mixture 1.0/2.0 12 weeks
Roy et al.
[183]
SD M Mixture 1.0 8 weeks
DeGuire et
al. [184]
SD F + M Mixture 1.0 16 weeks
de Almeida
et al. [185]
Wistar M Mixture 1.5 9 weeks
Lipids
1 3
Table 3 Summary of human studies on conjugated linoleic acid (CLA) and body composition
References Subject CLA supplementation ResultsdEnergy expendi-
turee
Other comments
Characteristic GenderaFormbDose (g/day) Duration BW BFM LBM
Berven et al. [186]Overweight/obese F + M Mixture 3.4 12 weeks – –
Blankson et al.
[114]
Overweight/obese F + M Mixture 1.7/3.5/5.1/6.8 6 and 12 weeks 1.7, 3.4 and 6.8
at 12 weeks
6.8 at 12 weeks
Zambell et al. [63]Normal F Mixture 2.5 9 weeks RMR/ REM
Kreider et al. [115]Normal/over-
weight
M Mixture 6.0 4 weeks
Riserus et al. [187]Obese M Mixture/t10c12 3.4 12 weeks by t10c12 by Mixture and
t10c12
Subjects with meta-
bolic syndrome
Kamphuis et al.
[28]
Overweight F + M Mixture 1.8/3.6 13 weeks ↓ ↑ ↑ RMR Weight regain
Gaullier et al. [29]Overweight F + M Mixture (TAG/
Free form)
3.6/3.4 1 year ↓ ↓ EE Free-form increased
LBM/ food
intake
Malpuech-Buru-
gere et al. [47]
Overweight F + M TAG of c9t11 and
t10c12
1.5/3.0 18 weeks Food intake
Riserus et al. [188]Obese M TAG of c9t11 3.0 12 weeks – –
Gaullier et al. [45]Overweight F + M Mixture (TAG/
Free form)
3.6/3.4 2 year ↓ ↓ 1-year extension
open study/ food
intake
Colakoglu et al.
[116]
Normal F Mixture 3.6 6 weeks ↓ ↓
Larsen et al. [189]Overweight/obese F + M Mixture 3.4 1 year Weight regain/
hypocaloric diet
Pinkoski et al. [61]Unknown F + M Mixture 5.0 7 weeks ↓ ↑ ↔ RMR Protein degrada-
tion
Gaullier et al. [30]Overweight/obese F + M Mixture 3.4 6 months ↓ ↑ Calorie intake
Lambert et al. [62]Normal/over-
weight
F + M Mixture 2.6 12 weeks RMR Appetite
Laso et al. [190]Overweight/obese F + M Mixture 3.0 12 weeks
Nazare et al. [59]Normal/over-
weight
F + M Mixture (TAG) 2.8 14 weeks RMR Food intake
Steck et al. [33]Obese F + M Mixture 3.2/6.4 12 weeks ↑ ↔ RMR/ RQ
Tarnopolsky et al.
[117]
Normal/over-
weight
F + M Mixture 5.4 + 5 g creatine
mono-hydrate
6 months ↓ ↑ Co-supplementation/
aging study model
Watras et al. [48]Overweight F + M Mixture 3.2 6 months ↓ ↓ RMR Energy intake
Diaz et al. [118]Overweight/obese F Mixture 1.8 + 0.4 mg cre-
atine picol-inate
12 weeks – Co-supplementation/
premenopausal
Park et al. [191]Overweight/obese F + M Mixture 2.4 8 weeks – – Food intake
Sneddon et al. [34]Normal/obese M Mixture 2.3 + 1.3 g ω-3
fatty acid
12 weeks Co-supplementation/
crossover design
Lipids
1 3
a F Female, M male
b Mixture, a mixed isomer of cis-9,trans-11 and trans-10,cis-12; c9t11, cis-9,trans-11 CLA isomer; t10c12,trans-10,cis-12 CLA isomer; TAG, triglyceride form; Free form, free fatty acid form
c Green tea, standardized for 45 % epigallocatechin gallate and 90 % polyphenol; BCAA, branched-chain amino acid
d BW body weight, BFM body fat mass, LBM lean body mass; no change, increase, decrease. All changes are based on significant differences between or within groups as reported in pub-
lications
e EE energy expenditure, RER respiratory energy ratio, RMR resting metabolic rate, RQ respiratory quotient, no change
Table 3 continued
References Subject CLA supplementation ResultsdEnergy expendi-
turee
Other comments
Characteristic GenderaFormbDose (g/day) Duration BW BFM LBM
Norris et al. [192]Obese F Mixture 6.4 16 weeks ↓ ↓ Type 2 diabetes/post-
menopausal
Raff et al. [31]Normal/over-
weight/obese
F Mixture/c9t11 5.5/4.7 16 weeks by Mixture by Mixture Postmenopausal
Cornish et al. [46]Obese F + M Mixture 4.3 + 9 g cre-
atine mono-
hydrate + 36 g
whey protein
5 weeks ↑ ↔ Energy intake
Racine et al. [32]Overweight/obese F + M Mixture (TAG) 2.4 7 months ↓ ↓ Childhood model
Joseph et al. [193]Overweight/obese M Mixture/c9t11 2.8/2.7 8 weeks Crossover design
Chen et al. [119]Overweight/obese F + M Mixture 1.7 12 weeks ↓ ↓
Macaluso et al.
[126]
Normal/over-
weight
M Mixture 4.8 3 weeks Crossover design/
serum testoster-
one
Lopez-Plaza et al.
[194]
Overweight F + M Mixture 3.0 24 weeks ↓ ↓
Shadman et al.
[195]
Overweight F + M Mixture 2.4 + 100 IU/day
vitamin E
8 weeks Co-supplementation/
type 2 diabetes
Ormsbee et al.
[196]
Overweight/obese F + M Mixture CLA + Green
tea + BCAAc
8 weeks – – Co-supplementation
Lipids
1 3
increase BMR (as resting metabolic rate, RMR) [28, 48,
59, 60], although other studies found no influence of CLA
on BMR, regardless of changes in body composition [33,
6163].
As part of the increased expenditure of energy, CLA sup-
plementation may increase thermogenesis, as evidenced by
the upregulation of uncoupling proteins (UCPs) expressed
in various tissues, such as the adipose, liver, and the skel-
etal muscle in mice and rats [38, 40, 55, 56, 6466]. UCP1
through UCP5 are mitochondrial proteins involved in the
combustion of stored or excess energy into heat. They are
expressed in distinct tissues in the body, and are responsible
for adaptive thermogenesis. Thus, an increase in UCPs by
CLA suggests that CLA may increase energy expenditure
by enhancing thermogenesis [67]. Likewise, physical activ-
ity also contributes to the overall expenditure of energy.
Studies in rodents have reported that CLA supplementation
increased energy expenditure in part by increasing the level
of physical activity [43, 56, 68], although human studies
are inconsistent in this regard [59, 61, 69].
In addition, fatty acid β-oxidation may contribute to
reducing body fat mass by using fat as an energy source,
rather than storing it in the body. Increased fat oxidation
in CLA-fed animals has been reported, as measured either
by reduced respiratory quotient or by increased activ-
ity and/or the expression of carnitine palmitoyltransferase
1 (CPT-1) in the skeletal muscle [12, 21, 41, 55, 56, 68,
7074]. Intriguingly, Close et al. [60] reported that human
subjects who received supplements with 4 g of CLA mix-
ture for 6 months had significantly increased fat oxidation
and energy expenditure during sleep. In another study,
CLA was found to potentiate adipocyte apoptosis, reduce
fat uptake, and/or modulate adipokine production, all of
which collectively contributed to the effective reduction
of fat accumulation [17]. At the same time, CLA increased
lean mass, which is an important observation, suggesting
that CLA targets skeletal muscle metabolism. The potential
effects of CLA on skeletal muscle metabolism, however,
have been less investigated.
CLA and Skeletal Muscle Metabolism
Skeletal muscle typically accounts for nearly 40 % of total
body mass, and acts as a significant regulator in overall
energy metabolism [75]. Muscle metabolism is a term used
to describe the complex biochemical reactions associated
with skeletal muscle function and development.
Overview of Muscle Energy Metabolism
The process of energy production for skeletal muscle is
tightly regulated by the type, intensity, and duration of
muscle exercise [76, 77]. Glycolysis is the catabolic pathway
for glucose in the cytosol under both anaerobic (absence of
oxygen) and aerobic (presence of oxygen) conditions. Aero-
bic glycolysis is an efficient means of producing adenosine
triphosphate (ATP) through mitochondrial oxidative phos-
phorylation, while anaerobic glycolysis produces an energy
supply with a much lower yield (36–38 ATPs produced by
aerobic glycolysis vs. 2 ATPs by anaerobic glycolysis). Dur-
ing high-intensity exercise, anaerobic metabolic pathways
are important, as aerobic metabolism alone may not be
adequate to meet energy demands, especially when there is
insufficient oxygen supply [7880]. In contrast, low-inten-
sity endurance exercise (requiring less than 60 % of maximal
oxygen uptake) such as jogging and swimming consumes
glucose and fatty acids as the primary energy sources dur-
ing the first hour, and then relies on stored intramuscular
and adipose tissue triglycerides for energy [81]. Thus it is
believed that prolonged endurance exercise is the more effi-
cient way to consume stored body fat.
Adaptive Responses of Skeletal Muscle
The skeletal muscle tissue also demonstrates metabolic
plasticity in response to altered external and internal condi-
tions, such as nutrient deprivation during fasting or calorie
restriction and contractile activity including exercise [82].
One of the adaptive responses of the muscle is the ability
to change the fiber type to meet energy demands. Muscle
fiber in humans is composed of three myosin heavy chain
(MHC) isoforms: MHC I, MHC IIa, and MHC IIx/d or IIb.
MHC I are slow-twitch type I fibers, which have greater
mitochondrial content, oxidative capacity, and resistance
to fatigue, using fatty acids as a main energy source. Fast-
twitch type II fibers (especially type IIb) are classified as
glycolytic fibers, since they use glucose and phosphocre-
atine as primary energy sources. Type IIa is an intermediate
type between type I and type IIb [83]. In response to exer-
cise, the skeletal muscle remodels its fiber type between
oxidative slow-twitch and glycolytic fast-twitch [84] in
correlation with the contractile properties and the physi-
ological and metabolic characteristics [85]. For example,
an endurance exercise triggers fiber type remodeling from
glycolytic fast-twitch to oxidative slow-twitch [84]. These
adaptations in the skeletal muscle are accompanied by an
increase in mitochondrial biogenesis, with the alteration
of mitochondrial volume (content per gram of tissue) and
composition (protein-to-lipid ratio in the inner mitochon-
drial membrane) [86].
Molecular Responses of Skeletal Muscle Metabolism
A number of regulators participate in the above-described
adaptive responses in skeletal muscle. Among them,
Lipids
1 3
AMP-activated protein kinase (AMPK) is the prime ini-
tial sensor of fuel and energy status in the skeletal muscle
(Scheme 1) [87]. An increase in intracellular AMP concen-
tration causes a shift to an increased AMP/ATP ratio, and
AMPK is then activated to provide the needed energy in
the cell. An activated AMPK deactivates acetyl-CoA car-
boxylase (ACC) by phosphorylation, inhibits the synthe-
sis of malonyl-CoA from two acetyl-CoAs, and results in
the activation of carnitine palmitoyltransferase 1 (CPT1), a
rate-limiting enzyme for fatty acid β-oxidation in mitochon-
dria. AMPK also induces metabolic changes including an
increase in glucose uptake by the induction of glucose trans-
porter type 4 (GLUT4), translocation in the skeletal muscle,
and a decrease in the rate of glycogen synthesis through
the phosphorylation of glycogen synthase [82]. Similar to
AMPK, sirtuin 1 (SIRT1, a conserved nicotinamide adenine
dinucleotide [NAD]+-dependent deacetylase) acts as a sen-
sor of metabolic stimuli (such as stress, starvation, or calorie
restriction) [88]. SIRT1 also regulates several transcriptional
factors (including protein 53, forkhead box O, and nuclear
factor κ-light-chain-enhancer of activated B cells, NFκB),
and is known to be involved in longevity [88]. Both AMPK
and SIRT1 may coherently mediate the response at the cellu-
lar level to the metabolic stimuli in the skeletal muscle [89].
Peroxisome proliferator-activated receptor γ coactivator
1α (PGC-1α), a downstream target of AMPK and SIRT1,
regulates several downstream transcription factors, includ-
ing peroxisome proliferator-activated receptor δ (PPARδ),
nuclear respiratory factor-1 and -2 (NRF), estrogen-
related receptor α (ERRα), and myocyte enhancer factor
2 (MEF2). These factors are important in initiating mito-
chondrial biogenesis and inducing fiber type transformation
in the skeletal muscle [90, 91]. Further support for the
significance of PGC-1α was provided in a study reporting
that ectopically expressing PGC-1α in the skeletal muscle
of transgenic mice induced the muscle fiber conversion of
glycolytic fast-twitch type II fibers into oxidative slow-
twitch type I fibers [92]. In a similar manner, the overex-
pression of PPARδ (a downstream regulator of PGC-1α)
resulted in the development of slow-twitch type I fibers
in skeletal muscle [93, 94]. The signaling cascade AMPK
to PPARδ via PGC-1α is an important metabolic pathway
involved in adaptive metabolism in the skeletal muscle.
As such, we have focused primarily on this pathway to
uncover the potential mechanism of CLA in skeletal mus-
cle metabolism.
Overall Effects of CLA on Skeletal Muscle Metabolism
Previous studies using mouse models have clearly sug-
gested that CLA is associated with a significant quanti-
tative increase in lean mass [12, 95]. In addition, CLA
supplementation up-regulates CPT1 and UCP2 from the
skeletal muscle, suggesting that an overall increase in
energy expenditure and fatty acid oxidation with CLA may
contribute to the reduction in fat accumulation [52, 56, 95,
96]. CLA has also been reported to prevent age-associated
skeletal muscle loss in aged rodents [19, 97]. The preven-
tive role of CLA in muscle is further supported by our
results in Fig. 1 with animals known to develop inactivity-
induced obesity with muscle dystrophy. When a cognate
of CLA (conjugated nonadecadienoic acid, known to have
biological effects similar to those of CLA) was given to
these animals, we observed an increase in voluntary activ-
ity and a reduction in body fat, as well as an increase in
muscle size, suggesting that this treatment may have pre-
vented muscle dystrophy typically associated with these
animals [56, 98].
Effects of CLA on Adaptive Muscle Responses
There is currently limited evidence demonstrating the role
of CLA in skeletal muscle metabolism [19, 21, 66, 99
102]. Supplementation of 1.2–2.0 % CLA in the diet of
pigs was found to significantly increase expression levels
of oxidative slow-twitch type I fiber, but did not increase
the expression of glycolytic fast-twitch type IIb and IIx
fibers in the pig’s skeletal muscle [103]. However, fiber
type changes are dependent on the growth phase in pigs
[104]. Similarly, Parra et al. [100] observed no CLA effect
on PPARδ and muscle fiber change in mice. Given these
limited studies, it cannot be conclusively stated that CLA
promotes muscle fiber type transformation. However, along
with the observation that CLA is linked to improved max-
imum endurance capacity in mice, it is highly likely that
EXERCISE
AMP:ATP
PPAR
PGC-1
AMPK
Mitochondria
biogenesis
Lipid
metabolism
SIRT1
Fiber type
transformation
CLA
Scheme 1 Proposed mechanism of CLA on muscle metabolism.
AMPK AMP-activated protein kinase, CLA conjugated linoleic acid,
SIRT1 silent information regulator two protein 1, PGC-1α peroxi-
some proliferator-activated receptor γ coactivator 1α, PPARδ per-
oxisome proliferator-activated receptor δ (Used with permission of
UMass Amherst)
Lipids
1 3
CLA influences muscle fiber type transformation [21, 68,
105, 106]. The effect of CLA on physical activity is further
discussed below.
Effects of CLA on Molecular Responses of Muscle
Metabolism
Several studies have reported the effects of CLA on the bio-
chemical alteration of several molecular markers of mus-
cle metabolism [19, 21, 66, 99102]. CLA treatment was
shown to activate AMPK in murine skeletal muscle cells
[107110], which negatively regulated ACC and enhanced
fatty acid β-oxidation [107, 110]. One study reported that
the cis-9,trans-11 CLA isomer activated AMPK at lower
concentrations (~50 μM), while the trans-10,cis-12 isomer
gradually activated AMPK in a dose-dependent manner up
to 120 μM, and then plateaued [108]. However, the effect
of CLA on SIRT1 activity in the skeletal muscle is cur-
rently not known [109].
CLA treatment did not affect the activity of PGC-1α, a
primary regulator in mitochondrial biogenesis, even when
the mitochondrial content in the human skeletal mus-
cle cells was increased by CLA [101]. Similarly, CLA-
fed mice and rats demonstrated no significant differences
in PGC-1α compared to control groups [66, 100]. On the
other hand, CLA treatment significantly up-regulated
PGC-1α in murine skeletal muscle cells [109], support-
ing the contention that CLA supplementation significantly
up-regulates molecular biomarkers such as succinate dehy-
drogenase, cytochrome c oxidase, superoxide dismutase 2,
catalase, and glutathione peroxidase in the skeletal muscle,
which is related to increased ATP production and thermo-
genesis via improved oxidative phosphorylation and anti-
oxidative capacity in the rodent models [19, 66]. These
results suggest that further confirmation is needed as to
whether CLA treatment is associated with mitochondrial
biogenesis through PGC-1α. Thus, further investigation is
required, particularly in humans, for a better understand-
ing of the correlation between CLA supplementation and
muscle fiber type transformation. In addition, CLA—in
particular, trans-10,cis-12—increased PPARδ expression in
murine muscle cells and mice [21, 102]. While these results
suggest that CLA may target muscle metabolism, no mech-
anistic studies have been completed to determine whether
CLA directly or indirectly influences any of these molecu-
lar targets.
Effect of CLA on Physical Activity
Animal studies using CLA and exercise are summarized
in Table 4. Studies using mice showed consistent effects
of reduced body fat or increased lean mass. Moreover,
there was a significant improvement in the exercise out-
come with CLA treatment (Table 4) [21, 68, 105, 106,
111]. Specifically, Kim et al. [21] reported that the trans-
10,cis-12 isomer was responsible for this effect, but not
the cis-9,trans-11 isomer. This is consistent with the role
of the trans-10,cis-12 isomer as the active isomer in body
fat reduction [18]. In contrast, studies in rats observed no
additional or synergistic effects of CLA treatment and exer-
cise training on endurance capacity and lean body mass
[43, 112]. This discrepancy was previously recognized as
Fig. 1 A cognate of CLA, conjugated nonadecadienoic acid (CNA),
significantly prevented muscle dystrophy in animals with inactivity-
induced obesity. a The data show that CNA supplementation (light
gray bars) resulted in a reduced number of smaller muscles (less than
700 μm) and increased number of medium-sized muscles (between
1500 and 2100 μm) compared to controls (black bars). b CNA-fed
animals had significantly increased average muscle size compared to
Nhlh-2 knockout controls. *Significantly different at P < 0.05. Six-
week-old female Nhlh-2 KO mice were fed either a control or CNA-
containing diet (0.1 % w/w of diet) for 8 weeks [semi-purified pow-
der diet, TD07518 (Teklad; Harlan Laboratories/Envigo, Madison,
WI, USA) with "vitamin-free" tested casein to avoid the naturally
occurring CLA in casein was used]. The diet consisted of an AIN-93-
based diet with 20 % fat total as soybean oil. The thigh muscle, vas-
tus lateralis, was frozen in liquid nitrogen, and frozen muscles were
cut into 10-μm section using a Cryotome. The sections were stained
with hematoxylin and eosin in order to visualize the muscle, and
muscle size was measured (>500 fibers) with ImageJ software (NIH).
Numbers are mean ± S. E (n = 3)
Lipids
1 3
a consequence of the greater sensitivity of mice than of
rats to CLA, partly due to differences in the administered
CLA dose on a weight basis and/or differences in the phys-
iology of animals (in particular, male rats continuously
gain weight, and no significant effects of CLA have been
reported for body fat) [113].
There are currently 17 CLA human intervention studies
reporting on CLA with exercise, as summarized in Table 5.
Table 4 Summary of studies using conjugated linoleic acid (CLA) and exercise regimen in animals
a F female, M male
b Mixture, a mixed isomer of cis-9,trans-11 and trans-10,cis-12; c9t11, cis-9,trans-11 CLA isomer; t10c12,trans-10,cis-12 CLA isomer
c Dosage (%) denotes a designated weight percentage of CLA in diet
d BW body weight, BFM body fat mass, LBM lean body mass; no change, increase, decrease. All changes are based on significant differ-
ences between or within groups as reported in publications
e EE energy expenditure, RER respiratory energy ratio, no change
f CPT1 carnitine palmitoyltransferase 1, LPL Lipoprotein lipase, PPARδ peroxisome proliferator-activated receptor δ, UCP2 uncoupling protein
2
References Animal CLA supplementation ResultsdExercise
type
Muscle metabolism Exercise
outcome
Strain GenderaFormbDosagecDuration BW BFM LBM Energy
expendi-
turee
Biomark-
ersf
Mizunoya
et al. [68]
BALB/c
Mice
M Mixture 0.5 % 1 week Endurance
(swim-
ming and
running)
RER
Fat
oxida-
tion
LPL
Bhattacha-
rya et al.
[57]
BALB/c
Mice
M Mixture 0.4 % 14 weeks ↓ ↓ Endurance
(running)
EE
Di Felice
et al.
[197]
ICR Mice M Mixture 0.425 mg/
day
6 weeks Endurance
(running)
Muscle
hyper-
trophy
Banu et al.
[198]
C57BL/6
Mice
F Mixture 0.5 % 10 weeks ↓ ↓ Endurance
(running)
Zhang et
al. [199]
ICR Mice M Mixture 0.5 % 18 weeks Endurance
(swim-
ming)
Kim et al.
[105]
BALB/c
Mice
M Mixture 1.0 % 10 weeks Endurance
(running)
Kim et al.
[21]
129 Sv/J
Mice
M c9t11/
t10c12
0.5 % 6 weeks ↓ ↓ Endurance
(running)
CPT1/
UCP2/
PPARδ
by t10c12
Hur et al.
[111]
ICR Mice F Mixture 1.0 % 6 weeks ↓ ↓ Endurance
(running)
Barone et
al. [106]
BALB/c
Mice
M Mixture 0.5 % 6 weeks Endurance
(running)
Testos-
terone
Shen et al.
[200]
129 Sv/J
Mice
M t10c12 0.1 % 7 weeks ↓ ↓ Endurance
(running)
Mirand et
al. [201]
Wistar
Rats
M Mixture/
c9t11/
t10c12
1.0 % 6 weeks Endurance
(running)
Faulcon-
nier et al.
[202]
Wistar
Rats
M Mixture/
c9t11/
t10c12
1.0 % 6 weeks Endurance
(running)
Mirand et
al. [43]
Wistar
Rats
M Mixture/
c9t11/
t10c12
1.0 % 6 weeks by
Mix-
ture
Endurance
(running)
Salgado et
al. [112]
Wistar
Rats
F + M Mixture 0.5 % 10 weeks ↓ ↓ Endurance
(swim-
ming)
Lipids
1 3
Among them, ten studies tested exercise outcomes [46,
61, 114122]. Overall, the effect of CLA supplementation
on exercise outcome varied across studies; six reported
positive results [46, 61, 114, 116, 117, 120], while oth-
ers reported no difference [115, 118, 119, 121, 122]. Four
clinical trials evaluated the effect of CLA supplementation
on physical activity, without a regular exercise regime [30,
48, 123, 124]. Among them, one study reported improved
physical activity with CLA treatment over a period of
3 months [123]. In general, the studies were relatively
short-term in nature (with the exception of two, they were
less than 12 weeks in length), and thus no conclusion can
be drawn as to whether the lack of effect was due to the
limited supplementation periods or the ineffectiveness of
CLA.
Four studies in humans evaluated the effects of co-
supplementation of CLA with other supplements, such as
creatine monohydrate, chromium picolinate, whey protein,
or amino acids, along with exercise training [46, 117, 118,
125]. Two of these studies used CLA and creatine mono-
hydrate for short- (5 weeks) or long-term (6 months) dura-
tions, accompanied by resistance training, and reported
increased lean body mass and improved strength compared
to the control group [46, 117].
Interestingly, Macaluso et al. [126] conducted a clini-
cal trial to investigate the effect of CLA with resistance
training on serum testosterone levels. The authors reported
significantly increased serum testosterone and resistance
exercise capability with CLA supplementation, with no
significant change in body weight, fat mass, or lean body
mass. Others have reported that testosterone can improve
mitochondrial biogenesis and total energy expenditure, and
that CLA supplementation was found to promote endur-
ance capacity in trained mice via the upregulation of tes-
tosterone biosynthesis [106, 127]. Thus, it is possible that
CLA improves exercise outcome by modulating testoster-
one; however, the Macaluso et al. [126] study may have
been too short to have observed changes in body composi-
tion due to CLA. Generally, indications are that CLA may
influence muscle metabolism, but mechanistic studies are
currently lacking.
Potential Health Concerns of CLA
Based on the results of animal and human studies, four
aspects of CLA supplementation are of concern: insulin
sensitivity, oxidative stress, maternal milk fat, and liver
function. These topics have been previously reviewed in
detail [5, 14, 15]. Among these potential health concerns,
the effects of CLA on glucose metabolism may affect the
potential role of CLA in skeletal muscle metabolism, and
effects are inconsistent in both animal and human studies.
However, evidence suggests that the long-term use of CLA,
particularly as a mixture of the two main isomers, will
likely have no adverse influence on glucose metabolism [5,
45, 128].
Other health concerns associated with CLA do not
directly involve the skeletal muscle metabolism, although
this aspect is important in understanding the health impact
of CLA. Reports of human studies have consistently
linked CLA supplements to increased oxidative markers,
particularly isoprostanes, but not to other biomarkers [5,
129, 130]. It has been suggested that CLA itself might be
metabolized to structurally similar isoprostanes that cannot
be distinguished from the isoprostanes used as oxidative
markers [131, 132].
CLA is known to reduce body fat, and CLA supplemen-
tation has been reported to significantly reduce milk fat,
particularly in cows [133, 134]. A limited number of human
studies have reported none or minimal change in milk fat
content after short-term CLA supplementation (less than
5 days) [135137], and in light of the primary difference
in milk fat origin between ruminants and humans, CLA is
expected to have minimal effects on human milk fat [133,
134]. The long-term effects of CLA on human milk fat
have yet to be determined.
In animal studies, there have been consistent obser-
vations of an enlarged liver with CLA feeding, but mini-
mal changes have been reported in human studies [8, 65,
138142]. While it is likely that the effect of CLA on the
enlarged liver is specific to rodents, three human cases of
hepatitis have been associated with CLA [143145]. Thus,
close monitoring of CLA supplementation with regard to
the health of the liver will be important, particularly with
long-term use.
Conclusion
To date, most mechanistic studies of the effects of CLA
on body composition have focused on lipid metabo-
lism in the adipose tissue. At the same time, a growing
number of studies have highlighted the importance of
CLA with respect to skeletal muscle metabolism, with
effects including increased energy expenditure and
enhanced physical activity. However, mechanistic stud-
ies investigating the mechanism by which CLA modu-
lates skeletal muscle metabolism are very preliminary,
and further investigation of the mechanistic effects of
CLA on the skeletal muscle metabolism, including mito-
chondrial biogenesis and muscle fiber type transforma-
tion, is needed. We expect that knowledge of the effect
Lipids
1 3
Table 5 Summary of human studies determining effects of conjugated linoleic acid (CLA) and exercise
References Subject CLA supplementation ResultsdExercise type Muscle metabolism Exercise
outcome
Characteristic GenderaFormbDosagecDuration BW BFM LBM Energy
expenditureeBiomarkersf
Blankson et al.
[114]
Overweight/
obese
F + M Mixture 1.7/3.5/5.1/6.8 6 and
12 weeks
1.7, 3.4 and
6.8 at 12
week
6.8 at 12
week
Standardized
training
Thom et al.
[203]
Normal F + M Mixture 1.8 12 weeks Strenuous
Kreider et al.
[115]
Normal/over-
weight
M Mixture 6.0 4 weeks Resistance
Loeffelholz et
al. 2003
Overweight F + M Mixture 3.8 6 months Resistance
Colakoglu et al.
[116]
Normal F Mixture 3.6 6 weeks ↓ ↓ Endurance
Pinkoski et al.
[61]
Unknown F + M Mixture 5.0 7 weeks Resistance RMR
Adams et al.
[204]
Overweight/
obese
M Mixture 3.2 4 weeks Resistance
Nazare et al.
[59]
Normal/over-
weight
F + M Mixture
(TAG)
2.8 14 weeks Regular train-
ing
RMR
Tarnopolsky et
al. [117]
Normal/over-
weight
F + M Mixture 5.4 + 5 g
creatine
monohydrate
6 months Resistance
Diaz et al. [118]Overweight/
obese
F Mixture 1.8 + 0.4 mg
chromium
picolinate
12 weeks Endurance
Cornish et al.
[46]
Obese F + M Mixture 4.3 + 9 g cre-
atine monohy-
drate + 36 g
whey protein
5 weeks Resistance
Michishita et al.
[125]
Normal/over-
weight
F + M Mixture 1.6 + 1.52 g
amino acids
12 weeks Resistance
Chen et al.
[119]
Overweight/
obese
F + M Mixture 1.7 12 weeks ↓ ↓ – Resistance
Macaluso et al.
[126]
Normal/over-
weight
M Mixture 4.8 3 weeks Resistance Testos-
terone in
serum
Bulut et al.
[205]
Overweight M Mixture 3.0 4 weeks Endurance
Lipids
1 3
of CLA on muscle metabolism will help to elucidate the
preventive effects of CLA on obesity, along with current
knowledge of its effects on adipose tissue. This knowl-
edge will also support the potential application of CLA
in the prevention of age-associated muscle loss, such as
sarcopenia.
Acknowledgments The authors thank Ms. Jayne M. Storkson for
help preparing this manuscript and Dr. Deborah J. Good at the Vir-
ginia Polytechnic Institute and State University for providing Nhlh-2
knockout animals. This material is based on work supported in part
by the National Institute of Food and Agriculture, U.S. Department of
Agriculture, the Massachusetts Agricultural Experimental Station, and
the Department of Food Science under Project No. MAS00998 and
MAS00450. Yoo Kim was supported in part by the Charm Sciences
scholarship from the Department of Food Science, University of Mas-
sachusetts, Amherst. Dr. Yeonhwa Park is one of the inventors of CLA
use patents assigned to the Wisconsin Alumni Research Foundation.
References
1. Parodi PW (1999) Conjugated linoleic acid: the early years. In:
Yurawecz MP, Mossoba MM, Kramer JKG, Pariza MW, Nelson
GJ (eds) Advances in conjugated linoleic acid research. AOCS
Press, Urbana
2. Kepler CR, Hirons KP, McNeill JJ, Tove SB (1966) Intermedi-
ates and products of the biohydrogenation of linoleic acid by
Butyrinvibrio fibrisolvens. J Biol Chem 241(6):1350–1354
3. Kay JK, Mackle TR, Auldist MJ, Thomson NA, Bauman
DE (2004) Endogenous synthesis of cis-9, trans-11 conju-
gated linoleic acid in dairy cows fed fresh pasture. J Dairy Sci
87(2):369–378
4. Chin S, Liu W, Storkson J, Ha Y, Pariza M (1992) Dietary
sources of conjugated dienoic isomers of linoleic acid, a newly
recognized class of anticarcinogens. J Food Compos Anal
5(3):185–197
5. Park Y (2014) Chapter 37—Conjugated linoleic acid in human
health effects on weight control. In: Watson RR (ed) Nutrition
in the prevention and treatment of abdominal obesity. Academic
Press, Dublin
6. Zlatanos SN, Laskaridis K, Sagredos A (2008) Conjugated lin-
oleic acid content of human plasma. Lipids Health Dis 7:34.
doi:10.1186/1476-511X-7-34
7. Mele MC, Cannelli G, Carta G, Cordeddu L, Melis MP, Murru
E, Stanton C, Banni S (2013) Metabolism of c9 t11-conjugated
linoleic acid (CLA) in humans. Prostaglandins Leukot Essent
Fat Acids (PLEFA) 89(2):115–119
8. Dilzer A, Park Y (2012) Implication of conjugated linoleic acid
(CLA) in human health. Crit Rev Food Sci Nutr 52(6):488–513
9. Bhattacharya A, Banu J, Rahman M, Causey J, Fernandes G
(2006) Biological effects of conjugated linoleic acids in health
and disease. J Nutr Biochem 17(12):789–810
10. Wahle KW, Heys SD, Rotondo D (2004) Conjugated linoleic
acids: are they beneficial or detrimental to health? Prog Lipid
Res 43(6):553–587
11. US Food and Drug Administration (2015) Nutrition labeling:
Trans Fat Labeling. http://www.fda.gov/Food/GuidanceRegula-
tion/GuidanceDocumentsRegulatoryInformation/LabelingNu-
trition/ucm064904.htm#transfat. Accessed 26 Aug 2015
12. Park Y, Albright K, Liu W, Storkson J, Cook M, Pariza M
(1997) Effect of conjugated linoleic acid on body composition
in mice. Lipids 32(8):853–858
a F female, M male
b Mixture, a mixed isomer of cis-9,trans-11 and trans-10,cis-12; c9t11, cis-9,trans-11 CLA isomer; t10c12,trans-10,cis-12 CLA isomer
c Dosage (%) denotes a designated weight percentage of CLA in diet
d BW body weight, BFM body fat mass, LBM lean body mass; no change, increase, decrease. All changes are based on significant differences between or within groups as reported in pub-
lications
e GET gas exchange threshold, PWCFT physical working capacity at the fatigue threshold, RCP respiratory compensation point, RMR resting metabolic rate, VO2 max maximal oxygen uptake,
no change
f GLUT4 glucose transporter type 4
Table 5 continued
References Subject CLA supplementation ResultsdExercise type Muscle metabolism Exercise
outcome
Characteristic GenderaFormbDosagecDuration BW BFM LBM Energy
expenditureeBiomarkersf
Jenkins et al.
[121, 122]
Normal/over-
weight
M Mixture 5.63 6 weeks Endurance PWCFT
VO2 max
GET
RCP
Tsao et al. [69]Normal M Mixture 3.8 8 weeks Endurance RMR Glycogen
resynthesis/
GLUT4
Lipids
1 3
13. McCrorie TA, Keaveney EM, Wallace JM, Binns N, Liv-
ingstone MBE (2011) Human health effects of conjugated
linoleic acid from milk and supplements. Nutr Res Rev
24(02):206–227
14. Park Y (2009) Conjugated linoleic acid (CLA): good or bad
trans fat? J Food Compos Anal 22:S4–S12
15. Pariza M (2004) Perspective on the safety and effectiveness of
conjugated linoleic acid. Am J Clin Nutr 79(6):1132S–1136S
16. Park Y, Pariza MW (2007) Mechanisms of body fat modu-
lation by conjugated linoleic acid (CLA). Food Res Int
40(3):311–323
17. Kennedy A, Martinez K, Schmidt S, Mandrup S, LaPoint K,
McIntosh M (2010) Antiobesity mechanisms of action of conju-
gated linoleic acid. J Nutr Biochem 21(3):171–179
18. Park Y, Storkson J, Albright K, Liu W, Pariza M (1999) Evi-
dence that the trans-10, cis-12 isomer of conjugated lin-
oleic acid induces body composition changes in mice. Lipids
34(3):235–241
19. Rahman MM, Halade GV, El Jamali A, Fernandes G (2009)
Conjugated linoleic acid (CLA) prevents age-associated skeletal
muscle loss. Biochem Biophys Res Commun 383(4):513–518
20. Halade GV, Rahman MM, Fernandes G (2010) Differential
effects of conjugated linoleic acid isomers in insulin-resistant
female C57Bl/6J mice. J Nutr Biochem 21(4):332–337
21. Kim JH, Kim J, Park Y (2012) trans-10, cis-12 conjugated lin-
oleic acid enhances endurance capacity by increasing fatty acid
oxidation and reducing glycogen utilization in mice. Lipids
47(9):855–863
22. Stangl GI (2000) Conjugated linoleic acids exhibit a strong
fat-to-lean partitioning effect, reduce serum VLDL lipids
and redistribute tissue lipids in food-restricted rats. J Nutr
130(5):1140–1146
23. Dugan M, Aalhus J, Schaefer A, Kramer J (1997) The effect of
conjugated linoleic acid on fat to lean repartitioning and feed
conversion in pigs 77(4):723–725
24. Dugan M, Aalhus J, Jeremiah L, Kramer J, Schaefer A (1999)
The effects of feeding conjugated linoleic acid on subsequent
pork quality 79(1):45–51
25. Dunshea F, Ostrowska E, Muralitharan M, Cross R, Bauman
D, Pariza M, Skarie C (1998) Dietary conjugated linoleic acid
decreases back fat in finisher gilts. J Anim Sci 76(Suppl 1):131
26. Tischendorf F, Schöne F, Möckel P, Jahreis G (1999) The effect
of conjugated linoleic acid on porcine growth, body composi-
tion, and fatty acids distribution in backfat, muscle and liver. In:
Symposium Vitamine und Zusatzstoffe in der Ernährung von
Mensch und Tier, pp 244–249
27. Ostrowska E, Muralitharan M, Cross RF, Bauman DE, Dun-
shea FR (1999) Dietary conjugated linoleic acids increase
lean tissue and decrease fat deposition in growing pigs. J Nutr
129(11):2037–2042
28. Kamphuis MM, Lejeune MP, Saris WH, Westerterp-Plantenga
MS (2003) The effect of conjugated linoleic acid supplementa-
tion after weight loss on body weight regain, body composition,
and resting metabolic rate in overweight subjects. Int J Obes
27(7):840–847
29. Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik
H, Gudmundsen O (2004) Conjugated linoleic acid supple-
mentation for 1 y reduces body fat mass in healthy overweight
humans. Am J Clin Nutr 79(6):1118–1125
30. Gaullier J, Halse J, Høivik HO, Høye K, Syvertsen C, Nurmin-
iemi M, Hassfeld C, Einerhand A, O’Shea M, Gudmundsen O
(2007) Six months supplementation with conjugated linoleic
acid induces regional-specific fat mass decreases in overweight
and obese. Br J Nutr 97(03):550–560
31. Raff M, Tholstrup T, Toubro S, Bruun JM, Lund P, Straarup
EM, Christensen R, Sandberg MB, Mandrup S (2009)
Conjugated linoleic acids reduce body fat in healthy postmeno-
pausal women. J Nutr 139(7):1347–1352
32. Racine NM, Watras AC, Carrel AL, Allen DB, McVean JJ, Clark
RR, O’Brien AR, O’Shea M, Scott CE, Schoeller DA (2010)
Effect of conjugated linoleic acid on body fat accretion in over-
weight or obese children. Am J Clin Nutr 91(5):1157–1164
33. Steck SE, Chalecki AM, Miller P, Conway J, Austin GL, Hardin
JW, Albright CD, Thuillier P (2007) Conjugated linoleic acid
supplementation for twelve weeks increases lean body mass in
obese humans. J Nutr 137(5):1188–1193
34. Sneddon AA, Tsofliou F, Fyfe CL, Matheson I, Jackson DM,
Horgan G, Winzell MS, Wahle KWJ, Ahren B, Williams LM
(2008) Effect of a conjugated linoleic acid and omega-3 fatty
acid mixture on body composition and adiponectin. Obesity
16(5):1019–1024
35. Schoeller DA, Watras AC, Whigham LD (2009) A meta-analy-
sis of the effects of conjugated linoleic acid on fat-free mass in
humans. Appl Physiol, Nutr, Metab 34(5):975–978
36. Park Y, Albright KJ, Storkson JM, Liu W, Cook ME, Pariza
MW (1999) Changes in body composition in mice during
feeding and withdrawal of conjugated linoleic acid. Lipids
34(3):243–248
37. Pariza M, Park Y, Cook M (2001) The biologically active iso-
mers of conjugated linoleic acid. Prog Lipid Res 40(4):283–298
38. Ryder JW, Portocarrero CP, Song XM, Cui L, Yu M, Combat-
siaris T, Galuska D, Bauman DE, Barbano DM, Charron MJ,
Zierath JR, Houseknecht KL (2001) Isomer-specific antidia-
betic properties of conjugated linoleic acid—improved glucose
tolerance, skeletal muscle insulin action, and UCP-2 gene
expression. Diabetes 50(5):1149–1157
39. Gudbrandsen OA, Rodriguez E, Wergedahl H, Mørk S, Rese-
land JE, Skorve J, Palou A, Berge RK (2009) Trans-10, cis-
12-conjugated linoleic acid reduces the hepatic triacylglycerol
content and the leptin mRNA level in adipose tissue in obese
Zucker fa/fa rats. Br J Nutr 102(06):803–815
40. Choi JS, Jung MH, Park HS, Song J (2004) Effect of conjugated
linoleic acid isomers on insulin resistance and mRNA levels of
genes regulating energy metabolism in high-fat–fed rats. Nutri-
tion 20(11):1008–1017
41. Inoue N, Nagao K, Wang Y, Noguchi H, Shirouchi B, Yanagita
T (2006) Dietary conjugated linoleic acid lowered tumor necro-
sis factor-α content and altered expression of genes related to
lipid metabolism and insulin sensitivity in the skeletal muscle
of Zucker rats. J Agric Food Chem 54(20):7935–7939
42. Park Y, Albright KJ, Storkson JM, Liu W, Pariza MW (2010)
Effects of dietary conjugated linoleic acid (CLA) on spontane-
ously hypertensive rats. J Funct Foods 2(1):54–59
43. Mirand PP, Mosoni L, Arnal-Bagnard M, Faulconnier Y, Char-
digny J, Chilliard Y (2006) Dietary conjugated linoleic acid
has limited effects on tissue protein anabolism in sedentary and
exercising adult rats 46(6):621–632
44. Park Y, Albright K, Storkson J, Liu W, Pariza M (2007) Conju-
gated linoleic acid (CLA) prevents body fat accumulation and
weight gain in an animal model. J Food Sci 72(8):S612–S617
45. Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H,
Vik H, Gudmundsen O (2005) Supplementation with con-
jugated linoleic acid for 24 months is well tolerated by and
reduces body fat mass in healthy, overweight humans. J Nutr
135(4):778–784
46. Cornish SM, Candow DG, Jantz NT, Chilibeck PD, Little JP,
Forbes S, Abeysekara S, Zello GA (2009) Conjugated linoleic
acid combined with creatine monohydrate and whey protein
supplementation during strength training. Int J Sport Nutr
19(1):79
47. Malpuech-Brugère C, de Venne Verboeket-van, Wilhelmine
PHG, Mensink RP, Arnal M, Morio B, Brandolini M, Saebo
Lipids
1 3
A, Lassel TS, Chardigny JM, Sébédio JL (2004) Effects of two
conjugated linoleic acid isomers on body fat mass in overweight
humans. Obes Res 12(4):591–598
48. Watras A, Buchholz A, Close R, Zhang Z, Schoeller D (2006)
The role of conjugated linoleic acid in reducing body fat and
preventing holiday weight gain. Int J Obes 31(3):481–487
49. Thrush AB, Chabowski A, Heigenhauser GJ, McBride BW, Or-
Rashid M, Dyck DJ (2007) Conjugated linoleic acid increases
skeletal muscle ceramide content and decreases insulin sensi-
tivity in overweight, non-diabetic humans. Appl Physiol, Nutr,
Metab 32(3):372–382
50. Dhurandhar NV, Schoeller DA, Brown AW, Heymsfield SB,
Thomas D, Sorensen TI, Speakman JR, Jeansonne M, Allison
DB, Energy Balance Measurement Working Group (2015)
Response to ‘Energy balance measurement: when something is
not better than nothing’. Int J Obes (Lond) 39(7):1175–1176
51. West DB, Delany JP, Camet PM, Blohm F, Truett AA, Sci-
meca J (1998) Effects of conjugated linoleic acid on body fat
and energy metabolism in the mouse. Am J Physiol 275(3 Pt
2):R667–R672
52. West DB, Blohm FY, Truett AA, DeLany JP (2000) Conju-
gated linoleic acid persistently increases total energy expendi-
ture in AKR/J mice without increasing uncoupling protein gene
expression. J Nutr 130(10):2471–2477
53. Ohnuki K, Haramizu S, Ishihara K, Fushiki T (2001) Increased
energy metabolism and suppressed body fat accumulation in
mice by a low concentration of conjugated linoleic acid. Biosci
Biotechnol Biochem 65(10):2200–2204
54. Ohnuki K, Haramizu S, Oki K, Ishihara K, Fushiki T (2001) A
single oral administration of conjugated linoleic acid enhanced
energy metabolism in mice. Lipids 36(6):583–587
55. Park Y, Park Y (2010) Conjugated nonadecadienoic acid is more
potent than conjugated linoleic acid on body fat reduction. J
Nutr Biochem 21(8):764–773
56. Park Y, Park Y (2012) Conjugated fatty acids increase energy
expenditure in part by increasing voluntary movement in mice.
Food Chem 133(2):400–409
57. Bhattacharya A, Rahman MM, Sun D, Lawrence R, Mejia W,
McCarter R, O’Shea M, Fernandes G (2005) The combination
of dietary conjugated linoleic acid and treadmill exercise lowers
gain in body fat mass and enhances lean body mass in high fat-
fed male Balb/C mice. J Nutr 135(5):1124–1130
58. Nagao K, Wang Y, Inoue N, Han S, Buang Y, Noda T, Kouda
N, Okamatsu H, Yanagita T (2003) The 10trans, 12cis isomer
of conjugated linoleic acid promotes energy metabolism in
OLETF rats. Nutrition 19(7):652–656
59. Nazare J, Perrière, de la AB, Bonnet F, Desage M, Peyrat J,
Maitrepierre C, Louche-Pelissier C, Bruzeau J, Goudable J, Las-
sel T (2007) Daily intake of conjugated linoleic acid-enriched
yoghurts: effects on energy metabolism and adipose tissue gene
expression in healthy subjects. Br J Nutr 97(02):273–280
60. Close RN, Schoeller DA, Watras AC, Nora EH (2007) Conju-
gated linoleic acid supplementation alters the 6-mo change in
fat oxidation during sleep. Am J Clin Nutr 86(3):797–804
61. Pinkoski C, Chilibeck PD, Candow DG, Esliger D, Ewaschuk
JB, Facci M, Farthing JP, Zello GA (2006) The effects of con-
jugated linoleic acid supplementation during resistance training.
Med Sci Sports Exerc 38(2):339
62. Lambert EV, Goedecke JH, Bluett K, Heggie K, Claassen A,
Rae DE, West S, Dugas J, Dugas L, Meltzer S (2007) Conju-
gated linoleic acid versus high-oleic acid sunflower oil: effects
on energy metabolism, glucose tolerance, blood lipids, appetite
and body composition in regularly exercising individuals. Br J
Nutr 97(05):1001–1011
63. Zambell KL, Keim NL, Van Loan MD, Gale B, Benito P, Kelley
DS, Nelson GJ (2000) Conjugated linoleic acid supplementation
in humans: effects on body composition and energy expendi-
ture. Lipids 35(7):777–782
64. Ealey K, El-Sohemy A, Archer M (2002) Effects of dietary con-
jugated linoleic acid on the expression of uncoupling proteins in
mice and rats. Lipids 37(9):853–861
65. Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim HJ,
Tange T, Okuyama H, Kasai M, Ikemoto S, Ezaki O (2000)
Conjugated linoleic acid supplementation reduces adipose tis-
sue by apoptosis and develops lipodystrophy in mice. Diabetes
49(9):1534–1542
66. Choi JS, Koh I, Jung MH, Song J (2007) Effects of three differ-
ent conjugated linoleic acid preparations on insulin signalling,
fat oxidation and mitochondrial function in rats fed a high-fat
diet. Br J Nutr 98(2):264–275
67. Adams S, Pan G, Yu X (2001) Perspectives on the biology of
uncoupling protein (UCP) homologues. Biochem Soc Trans
29(5):100
68. Mizunoya W, Haramizu S, Shibakusa T, Okabe Y, Fushiki T
(2005) Dietary conjugated linoleic acid increases endurance
capacity and fat oxidation in mice during exercise. Lipids
40(3):265–271
69. Tsao J, Liao S, Korivi M, Hou C, Kuo C, Wang H, Cheng I
(2014) Oral conjugated linoleic acid supplementation enhanced
glycogen resynthesis in exercised human skeletal muscle. J
Sports Sci (ahead-of-print):1–9
70. Bouthegourd JC, Even PC, Gripois D, Tiffon B, Blouquit
MF, Roseau S, Lutton C, Tome D, Martin JC (2002) A CLA
mixture prevents body triglyceride accumulation with-
out affecting energy expenditure in Syrian hamsters. J Nutr
132(9):2682–2689
71. Degrace P, Demizieux L, Gresti J, Chardigny JM, Sebedio JL,
Clouet P (2004) Hepatic steatosis is not due to impaired fatty
acid oxidation capacities in C57BL/6J mice fed the conjugated
trans-10, cis-12-isomer of linoleic acid. J Nutr 134(4):861–867
72. Nagao K, Inoue N, Wang YM, Shirouchi B, Yanagita T (2005)
Dietary conjugated linoleic acid alleviates nonalcoholic fatty
liver disease in Zucker (fa/fa) rats. J Nutr 135(1):9–13
73. Peters JM, Park Y, Gonzalez FJ, Pariza MW (2001) Influence of
conjugated linoleic acid on body composition and target gene
expression in peroxisome proliferator-activated receptor α-null
mice 1533(3):233–242
74. Ribot J, Portillo MP, Picó C, Teresa Macarulla M, Palou A
(2007) Effects of trans-10, cis-12 conjugated linoleic acid on
the expression of uncoupling proteins in hamsters fed an athero-
genic diet. Br J Nutr 97(06):1074–1082
75. Salmons S, Henriksson J (1981) The adaptive response of skel-
etal muscle to increased use. Muscle Nerve 4(2):94–105
76. Hänninen O, Atalay M (1998) Oxidative metabolism in skel-
etal muscle. In: Anonymous oxidative stress in skeletal muscle,
Springer
77. Westerblad H, Bruton JD, Katz A (2010) Skeletal muscle:
energy metabolism, fiber types, fatigue and adaptability. Exp
Cell Res 316(18):3093–3099
78. Felig P, Wahren J (1975) Fuel homeostasis in exercise. N Engl J
Med 293(21):1078–1084
79. Wahren J (1977) Glucose turnover during exercise in man*.
Ann NY Acad Sci 301(1):45–55
80. Esséen B (1977) Intramuscular substrate utilization during pro-
longed exercise*. Ann NY Acad Sci 301(1):30–44
81. Sahlin K, Tonkonogi M, Söderlund K (1998) Energy supply and
muscle fatigue in humans. Acta Physiol Scand 162(3):261–266
82. Cantó C, Auwerx J (2010) AMP-activated protein kinase and its
downstream transcriptional pathways 67(20):3407–3423
83. Spangenburg E, Booth F (2003) Molecular regulation of
individual skeletal muscle fibre types. Acta Physiol Scand
178(4):413–424
Lipids
1 3
84. Schiaffino S, Reggiani C (2011) Fiber types in mammalian
skeletal muscles. Physiol Rev 91(4):1447–1531
85. Brooke MH, Kaiser KK (1970) Muscle fiber types: how many
and what kind? Arch Neurol 23(4):369–379
86. Hood DA, Irrcher I, Ljubicic V, Joseph A (2006) Coordina-
tion of metabolic plasticity in skeletal muscle. J Exp Biol
209(12):2265–2275
87. Hardie DG, Sakamoto K (2006) AMPK: a key sensor of fuel
and energy status in skeletal muscle. Physiology (Bethesda)
21:48–60
88. Kwon H, Ott M (2008) The ups and downs of SIRT1. Trends
Biochem Sci 33(11):517–525
89. Ruderman NB, Xu XJ, Nelson L, Cacicedo JM, Saha AK, Lan
F, Ido Y (2010) AMPK and SIRT1: a long-standing partnership?
Am J Physiol Endocrinol Metab 298(4):E751–E760
90. Lin J, Handschin C, Spiegelman BM (2005) Metabolic control
through the PGC-1 family of transcription coactivators. Cell
Metab 1(6):361–370
91. Olesen J, Kiilerich K, Pilegaard H (2010) PGC-1α-mediated
adaptations in skeletal muscle. Pflüg Arch-Eur J Physiol
460(1):153–162
92. Lin J, Wu H, Tarr PT, Zhang CY, Wu ZD, Boss O, Michael LF,
Puigserver P, Isotani E, Olson EN, Lowell BB, Bassel-Duby
R, Spiegelman BM (2002) Transcriptional co-activator PGC-1
alpha drives the formation of slow-twitch muscle fibres. Nature
418(6899):797–801
93. Luquet S, Lopez-Soriano J, Holst D, Fredenrich A, Melki J,
Rassoulzadegan M, Grimaldi PA (2003) Peroxisome prolifer-
ator-activated receptor delta controls muscle development and
oxidative capability. FASEB J. 17(15):2299–2301
94. Wang Y, Zhang C, Yu R, Cho H, Nelson M, Bayuga-Ocampo
C, Ham J, Kang H, Evans R (2004) Regulation of muscle
fiber type and running endurance by PPAR delta. PLoS Biol
2(10):1532–1539
95. Terpstra AH, Beynen AC, Everts H, Kocsis S, Katan MB, Zock
PL (2002) The decrease in body fat in mice fed conjugated lin-
oleic acid is due to increases in energy expenditure and energy
loss in the excreta. J Nutr 132(5):940–945
96. Kim JH, Gilliard D, Good DJ, Park Y (2012) Preventive effects
of conjugated linoleic acid on obesity by improved physical
activity in nescient basic helix-loop-helix 2 knockout mice dur-
ing growth period. Food Funct 3(12):1280–1285
97. Halade GV, Rahman MM, Fernandes G (2009) Effect of CLA
isomers and their mixture on aging C57Bl/6J mice. Eur J Nutr
48(7):409–418
98. Kim JH, Park Y, Kim D, Good DJ, Park Y (2013) Dietary conju-
gated nonadecadienoic acid prevents adult-onset obesity in nes-
cient basic helix-loop-helix 2 knockout mice. J Nutr Biochem
24(3):556–566
99. Kim Y, Kim D, Good DJ, Park Y (2015) Effects of post-wean-
ing administration of conjugated linoleic acid on development
of obesity in nescient basic helix-loop-helix 2 knockout mice. J
Agric Food Chem 63:5212–5223
100. Parra P, Serra F, Palou A (2012) Transcriptional analysis reveals
a high impact of conjugated linoleic acid on stearoyl-Coenzyme
A desaturase 1 mRNA expression in mice gastrocnemius mus-
cle. Genes Nutr 7(4):537–548
101. Vaughan RA, Garcia-Smith R, Bisoffi M, Conn CA, Trujillo
KA (2012) Conjugated linoleic acid or omega 3 fatty acids
increase mitochondrial biosynthesis and metabolism in skeletal
muscle cells. Lipids Health Dis 11:142
102. Oraldi M, Maggiora M, Paiuzzi E, Canuto RA, Muzio G
(2013) CLA Reduces inflammatory mediators from A427
human lung cancer cells and A427 conditioned medium pro-
motes differentiation of C2C12 murine muscle cells. Lipids
48(1):29–38
103. Huang J, Qi R, Chen X, You X, Liu X, Yang F, Liu Z (2014)
Improvement in the carcass traits and meat quality of growing-
finishing Rongchang pigs by conjugated linoleic acid through
altered gene expression of muscle fiber types. Genet Mol Res:
GMR 13(3):7061–7069
104. Men X, Deng B, Xu Z, Tao X, Qi K (2013) Age-related changes
and nutritional regulation of myosin heavy-chain composition in
longissimus dorsi of commercial pigs. Animal 7(09):1486–1492
105. Kim JH, Park HG, Pan JH, Kim SH, Yoon HG, Bae GS, Lee
H, Eom S, Kim YJ (2010) Dietary conjugated linoleic acid
increases endurance capacity of mice during treadmill exercise
13(5):1057–1060
106. Barone R, Macaluso F, Catanese P, Gammazza AM, Rizzuto
L, Marozzi P, Giudice GL, Stampone T, Cappello F, Morici
G (2013) Endurance exercise and Conjugated Linoleic Acid
(CLA) supplementation up-regulate CYP17A1 and stimulate
testosterone biosynthesis 8(11):e79686
107. Mohankumar SK, Taylor CG, Siemens L, Zahradka P (2013)
Activation of phosphatidylinositol-3 kinase, AMP-activated
kinase and Akt substrate-160 kDa by trans-10, cis-12 conju-
gated linoleic acid mediates skeletal muscle glucose uptake. J
Nutr Biochem 24(2):445–456
108. Mohankumar SK, Taylor CG, Siemens L, Zahradka P (2012)
Acute exposure of L6 myotubes to cis-9, trans-11 and trans-
10, cis-12 conjugated linoleic acid isomers stimulates glucose
uptake by modulating Ca2+/calmodulin-dependent protein
kinase II. Int J Biochem Cell Biol 44(8):1321–1330
109. Kim Y, Park Y (2015) Conjugated linoleic acid (CLA) stimu-
lates mitochondrial biogenesis signaling by the upregulation
of PPARγ coactivator 1α (PGC-1α) in C2C12 cells. Lipids
50(4):329–338
110. Qin H, Liu Y, Lu N, Li Y, Sun C (2009) cis-9, trans-11-conju-
gated linoleic acid activates AMP-activated protein kinase in
attenuation of insulin resistance in C2C12 myotubes. J Agric
Food Chem 57(10):4452–4458
111. Hur SJ, Kim DH, Chun SC, Lee SK (2013) Effects of dietary
conjugated linoleic acid and biopolymer encapsulation on lipid
metabolism in mice. Int J Mol Sci 14(4):6848–6862
112. Salgado JM, Ferreira TRB, Donado-Pestana CM, de Almeida
OC, Das Neves, Aline Mouro Ribeiro, Mansi DN, Dias, dos
Santos CT (2012) Conjugated linoleic acid combined with
physical activity reduces body fat accumulation but does not
modify lean body mass in male and female Wistar rats. J Med
Food 15(4):406–412
113. Park Y (1996) Regulation of energy metabolism and the cata-
bolic effects of immune stimulation by conjugated linocleic
acid
114. Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein
J, Gudmundsen O (2000) Conjugated linoleic acid reduces
body fat mass in overweight and obese humans. J Nutr
130(12):2943–2948
115. Kreider RB, Ferreira MP, Greenwood M, Wilson M, Almada
AL (2002) Effects of conjugated linoleic acid supplementation
during resistance training on body composition, bone density,
strength, and selected hematological markers. J Strength Cond
Res 16(3):325–334
116. Colakoglu S, Colakoglu M, Taneli F, Cetinoz F, Turkmen M
(2006) Cumulative effects of conjugated linoleic acid and exer-
cise on endurance development, body composition, serum lep-
tin and insulin levels. J Sports Med Phys Fit 46(4):570–577
117. Tarnopolsky M, Zimmer A, Paikin J, Safdar A, Aboud A, Pearce
E, Roy B, Doherty T (2007) Creatine monohydrate and conju-
gated linoleic acid improve strength and body composition fol-
lowing resistance exercise in older adults. PLoS One 2(10):e991
118. Diaz ML, Watkins BA, Li Y, Anderson RA, Campbell WW
(2008) Chromium picolinate and conjugated linoleic acid do
Lipids
1 3
not synergistically influence diet-and exercise-induced changes
in body composition and health indexes in overweight women. J
Nutr Biochem 19(1):61–68
119. Chen S, Lin Y, Huang H, Hsu W, Houng J, Huang C (2012)
Effect of conjugated linoleic acid supplementation on weight
loss and body fat composition in a Chinese population. Nutri-
tion 28(5):559–565
120. Macaluso F, Barone R, Catanese P, Carini F, Rizzuto L, Farina
F, Di Felice V (2013) Do fat supplements increase physical per-
formance? Nutrients 5(2):509–524
121. Jenkins NDM, Buckner SL, Baker RB, Bergstrom HC,
Cochrane KC, Weir JP, Housh TJ, Cramer JT (2014) Effects of
6 weeks of aerobic exercise combined with conjugated linoleic
acid on the physical working capacity at fatigue threshold. J
Strength Cond Res 28(8):2127–2135
122. Jenkins NDM, Buckner SL, Cochrane KC, Bergstrom HC,
Goldsmith JA, Weir JP, Housh TJ, Cramer JT (2014) CLA sup-
plementation and aerobic exercise lower blood triacylglycerol,
but have no effect on peak oxygen uptake or cardiorespiratory
fatigue thresholds. Lipids 49(9):871–880
123. Ha YL, Jeong SB (2010) Effects of conjugated linoleic acid on
body fat reduction and physical exercise enhancement of obese
male middle school students. J Life Sci 20:1844–1850
124. Tajmanesh M, Aryaeian N, Hosseini M, Mazaheri R, Kordi R
(2015) Conjugated linoleic acid supplementation has no impact
on aerobic capacity of healthy young men. Lipids:1–5
125. Michishita T, Kobayashi S, Katsuya T, Ogihara T, Kawabuchi
K (2010) Evaluation of the antiobesity effects of an amino acid
mixture and conjugated linoleic acid on exercising healthy over-
weight humans: a randomized, double-blind, placebo-controlled
trial. J Int Med Res 38(3):844–859
126. Macaluso F, Morici G, Catanese P, Ardizzone NM, Marino
Gammazza A, Bonsignore G, Lo Giudice G, Stampone T,
Barone R, Farina F, Di Felice V (2012) Effect of conjugated
linoleic acid on testosterone levels in vitro and in vivo after
an acute bout of resistance exercise. J Strength Cond Res
26(6):1667–1674
127. Usui T, Kajita K, Kajita T, Mori I, Hanamoto T, Ikeda T, Okada
H, Taguchi K, Kitada Y, Morita H (2014) Elevated mitochon-
drial biogenesis in skeletal muscle is associated with testos-
terone-induced body weight loss in male mice. FEBS Lett
588(10):1935–1941
128. Whigham L, O’shea M, Mohede I, Walaski H, Atkinson R
(2004) Safety profile of conjugated linoleic acid in a 12-month
trial in obese humans. Food Chem Toxicol 42(10):1701–1709
129. Pfeuffer M, Fielitz K, Laue C, Winkler P, Rubin D, Helwig U,
Giller K, Kammann J, Schwedhelm E, Boeger RH, Bub A, Bell
D, Schrezenmeir J (2011) CLA does not impair endothelial
function and decreases body weight as compared with safflower
oil in overweight and obese male subjects. J Am Coll Nutr
30(1):19–28
130. Kim J, Paik H, Shin M, Park E (2012) Eight weeks of conju-
gated linoleic acid supplementation has no effect on antioxidant
status in healthy overweight/obese Korean individuals. Eur J
Nutr 51(2):135–141
131. Banni S, Petroni A, Blasevich M, Carta G, Cordeddu L, Murru
E, Melis M, Mahon A, Belury M (2004) Conjugated linoleic
acids (CLA) as precursors of a distinct family of PUFA. Lipids
39(11):1143–1146
132. Turpeinen AM, Mutanen M, Aro A, Salminen I, Basu S,
Palmquist DL, Griinari JM (2002) Bioconversion of vaccenic
acid to conjugated linoleic acid in humans. Am J Clin Nutr
76(3):504–510
133. Bernard L, Leroux C, Chilliard Y (2008) Expression and nutri-
tional regulation of lipogenic genes in the ruminant lactating
mammary gland. Bioact Compon Milk 606:67–108
134. Bauman D, Griinari J (2003) Nutritional regulation of milk fat
synthesis. Annu Rev Nutr 23:203–227
135. Hasin A, Griinari JM, Williams JE, Shahin AM, McGuire
MA, McGuire MK (2007) Consumption of c9, t11–18: 2 or
t10, c12–18: 2 enriched dietary supplements does not influ-
ence milk macronutrients in healthy, lactating women. Lipids
42(9):835–843
136. Mosley SA, Shahin AM, Williams J, McGuire MA, McGuire
MK (2007) Supplemental conjugated linoleic acid consumption
does not influence milk macronutrient contents in all healthy
lactating women. Lipids 42(8):723–729
137. Masters N, McGuire MA, Beerman KA, Dasgupta N, McGuire
MK (2002) Maternal supplementation with CLA decreases
milk fat in humans. Lipids 37(2):133–138
138. Belury MA, Kempa-Steczko A (1997) Conjugated linoleic
acid modulates hepatic lipid composition in mice. Lipids
32(2):199–204
139. Jaudszus A, Moeckel P, Hamelmann E, Jahreis G (2010)
Trans-10, cis-12-CLA-caused lipodystrophy is associated with
profound changes of fatty acid profiles of liver, white adi-
pose tissue and erythrocytes in mice: possible link to tissue-
specific alterations of fatty acid desaturation. Ann Nutr Metab
57(2):103–111
140. Larsen TM, Toubro S, Astrup A (2003) Efficacy and safety of
dietary supplements containing CLA for the treatment of obe-
sity: evidence from animal and human studies. J Lipid Res
44(12):2234–2241
141. Onakpoya IJ, Posadzki PP, Watson LK, Davies LA, Ernst E
(2012) The efficacy of long-term conjugated linoleic acid
(CLA) supplementation on body composition in overweight and
obese individuals: a systematic review and meta-analysis of ran-
domized clinical trials. Eur J Nutr 51(2):127–134
142. Wanders AJ, Leder L, Banga JD, Katan MB, Brouwer IA
(2010) A high intake of conjugated linoleic acid does not affect
liver and kidney function tests in healthy human subjects. Food
Chem Toxicol 48(2):587–590
143. Ramos R, Mascarenhas J, Duarte P, Vicente C, Casteleiro C
(2009) Conjugated linoleic acid-induced toxic hepatitis: first
case report. Dig Dis Sci 54(5):1141–1143
144. Nortadas R, Barata J (2012) Fulminant hepatitis during
self-medication with conjugated linoleic acid. Ann Hepatol
11(2):265–267
145. Bilal M, Patel Y, Burkitt M, Babich M (2015) Linoleic acid
induced acute hepatitis: a case report and review of the litera-
ture. Case Reports Hepatol 2015:807354
146. DeLany JP, Blohm F, Truett AA, Scimeca JA, West DB (1999)
Conjugated linoleic acid rapidly reduces body fat content in
mice without affecting energy intake. Am J Physiol 276(4 Pt
2):R1172–R1179
147. Park Y, Pariza MW (2001) Lipoxygenase inhibitors inhibit hep-
arin-releasable lipoprotein lipase activity in 3T3-L1 adipocytes
and enhance body fat reduction in mice by conjugated linoleic
acid. Biochim et Biophys Acta (BBA)-Mol Cell Biol Lipids
1534(1):27–33
148. Park Y, Pariza MW (2001) The effects of dietary conju-
gated nonadecadienoic acid on body composition in mice.
Biochim et Biophys Acta (BBA)-Mol Cell Biol Lipids
1533(3):171–174
149. Ntambi JM, Choi Y, Park Y, Peters JM, Pariza MW (2002)
Effects of conjugated linoleic acid (CLA) on immune responses,
body composition and stearoyl-CoA desaturase. Can J Appl
Physiol 27(6):617–627
150. Hayman A, MacGibbon A, Pack RJ, Rutherfurd K, Green JH
(2002) High intake, but not low intake, of CLA impairs weight
gain in growing mice. Lipids 37(7):689–692
Lipids
1 3
151. Warren JM, Simon VA, Bartolini G, Erickson KL, Mackey BE,
Kelley DS (2003) Trans-10, cis-12 CLA increases liver and
decreases adipose tissue lipids in mice: possible roles of spe-
cific lipid metabolism genes. Lipids 38(5):497–504
152. Chardigny JM, Hasselwander O, Genty M, Kraemer K,
Ptock A, Sededio JL (2003) Effect of conjugated FA on
feed intake, body composition, and liver FA in mice. Lipids
38(9):895–902
153. Terpstra AHM, Javadi M, Beynen AC, Kocsis S, Lankhorst
AE, Lemmens AG, Mohede ICM (2003) Dietary conjugated
linoleic acids as free fatty acids and triacylglycerols similarly
affect body composition and energy balance in mice. J Nutr
133(10):3181–3186
154. Hargrave KM, Meyer BJ, Li C, Azain MJ, Baile CA, Miner
JL (2004) Influence of dietary conjugated linoleic acid and
fat source on body fat and apoptosis in mice*. Obes Res
12(9):1435–1444
155. Park Y, Storkson JM, Liu W, Albright KJ, Cook ME, Pariza
MW (2004) Structure–activity relationship of conjugated lin-
oleic acid and its cognates in inhibiting heparin-releasable
lipoprotein lipase and glycerol release from fully differentiated
3T3-L1 adipocytes. J Nutr Biochem 15(9):561–568
156. Javadi M, Beynen AC, Hovenier R, Lankhorst AE, Lemmens
AG, Terpstra AHM, Geelen MJH (2004) Prolonged feed-
ing of mice with conjugated linoleic acid increases hepatic
fatty acid synthesis relative to oxidation. J Nutr Biochem
15(11):680–687
157. Ohashi A, Matsushita Y, Shibata H, Kimura K, Miyashita K,
Saito M (2004) Conjugated linoleic acid deteriorates insulin
resistance in obese/diabetic mice in association with decreased
production of adiponectin and leptin. J Nutr Sci Vitaminol
50(6):416–421
158. Javadi M, Everts H, Hovenier R, Kocsis S, Lankhorst AE, Lem-
mens AG, Schonewille JT, Terpstra AHM, Beynen AC (2004)
The effect of six different C18 fatty acids on body fat and
energy metabolism in mice. Br J Nutr 92(3):391–399
159. Park Y, Storkson JM, Albright KJ, Liu W, Pariza MW (2005)
Biological activities of conjugated fatty acids: conjugated eico-
sadienoic (conj. 20: 2 Delta (c11, t13/t12, c14)) eicosatrienoic
(conj. 20: 3 Delta (c8, t12, c14)) and heneicosadienoic (conj.
21: 2 Delta (c12, t144/c13, t15)) acids and other metabolites of
conjugated linoleic acid. Biochim et Biophys Acta (BBA)-Mol
Cell Biol Lipids 1687(1–3):120–129
160. de Roos B, Rucklidge G, Reid M, Ross K, Duncan G, Nav-
arro MA, Arbones-Mainar JM, Guzman-Garcia MA, Osada J,
Browne J, Loscher CE, Roche HM (2005) Divergent mecha-
nisms of cis9, trans11-and trans10, cis12-conjugated linoleic
acid affecting insulin resistance and inflammation in apoli-
poprotein E knockout mice: a proteomics approach. FASEB J
19(9):1746
161. Hargrave KM, Azain MJ, Miner JL (2005) Dietary coconut oil
increases conjugated linoleic acid-induced body fat loss in mice
independent of essential fatty acid deficiency. Biochim et Bio-
phys Acta (BBA)-Mol Cell Biol Lipids 1737(1):52–60
162. Winzell MS, Pacini G, Ahren B (2006) Insulin secretion after
dietary supplementation with conjugated linoleic acids and n-3
polyunsaturated fatty acids in normal and insulin-resistant mice.
Am J Physiol-Endocrinol Metab 290(2):E347–E354
163. Bhattacharya A, Rahman MM, McCarter R, O’Shea M, Fer-
nandes G (2006) Conjugated linoleic acid and chromium lower
body weight and visceral fat mass in high-fat-diet-fed mice.
Lipids 41(5):437–444
164. Viswanadha S, McGilliard ML, Herbein JH (2006) Desatu-
ration indices in liver, muscle, and bone of growing male and
female mice fed trans-10, cis-12 conjugated linoleic acid.
Lipids 41(8):763–770
165. Rahman MM, Bhattacharya A, Banu J, Fernandes G (2007)
Conjugated linoleic acid protects against age-associated bone
loss in C57BL/6 female mice. J Nutr Biochem 18(7):467–474
166. Javadi M, Geelen MJH, Everts H, Lemmens AG, Beynen AC
(2007) Body composition and selected blood parameters in
mice fed a combination of fibre and conjugated linoleic acid. J
Anim Physiol Anim Nutr 91(11–12):492–497
167. Hur S, Whitcomb F, Rhee S, Park Y, Good DJ, Park Y (2009)
Effects of trans-10, cis-12 conjugated linoleic acid on body
composition in genetically obese mice. J Med Food 12(1):56–63
168. Andreoli MF, Gonzalez MA, Martinelli MI, Mocchiutti NO,
Bernal CA (2009) Effects of dietary conjugated linoleic acid at
high-fat levels on triacylglycerol regulation in mice. Nutrition
25(4):445–452
169. Moon H, Lee H, Seo J, Chung C, Kim T, Choi Y, Cho C (2009)
Antiobesity effect of PEGylated conjugated linoleic acid on
high-fat diet-induced obese C57BL/6J (ob/ob) mice: attenuation
of insulin resistance and enhancement of antioxidant defenses. J
Nutr Biochem 20(3):187–194
170. Parra P, Serra F, Palou A (2010) Moderate doses of conjugated
linoleic acid isomers mix contribute to lowering body fat con-
tent maintaining insulin sensitivity and a noninflammatory pat-
tern in adipose tissue in mice. J Nutr Biochem 21(2):107–115
171. Halade GV, Rahman MM, Williams PJ, Fernandes G (2011)
Combination of conjugated linoleic acid with fish oil prevents
age-associated bone marrow adiposity in C57Bl/6 J mice. J
Nutr Biochem 22(5):459–469
172. Park Y, Terk M, Park Y (2011) Interaction between dietary con-
jugated linoleic acid and calcium supplementation affecting
bone and fat mass. J Bone Miner Metab 29(3):268–278
173. Fedor DM, Adkins Y, Newman JW, Mackey BE, Kelley DS
(2013) The Effect of docosahexaenoic acid on t 10, c 12-con-
jugated linoleic acid-induced changes in fatty acid composition
of mouse liver, Adipose, and Muscle. Metab Syndr Relat Disord
11(1):63–70
174. Scalerandi MV, Gonzalez MA, Saín J, Fariña AC, Bernal CA
(2014) Effect of conjugated linoleic acid mixtures and different
edible oils on body composition and lipid regulation in mice.
Nutr Hosp 3(29):591–601
175. Azain MJ, Hausman DB, Sisk MB, Flatt WP, Jewell DE (2000)
Dietary conjugated linoleic acid reduces rat adipose tissue cell
size rather than cell number. J Nutr 130(6):1548–1554
176. Sisk MB, Hausman DB, Martin RJ, Azain MJ (2001) Dietary
conjugated linoleic acid reduces adiposity in lean but not obese
Zucker rats. J Nutr 131(6):1668–1674
177. Kim MR, Park Y, Albright KJ, Pariza MW (2002) Differ-
ential responses of hamsters and rats fed high-fat or low-fat
diets supplemented with conjugated linoleic acid. Nutr Res
22(6):715–722
178. Yamazaki N, Yamanaka Y, Hashimoto Y, Shinohara Y, Shima
A, Terada H (1997) Structural features of the gene encoding
human muscle type carnitine palmitoyltransferase I. FEBS Lett
409(3):401–406
179. Henriksen EJ, Teachey MK, Taylor ZC, Jacob S, Ptock A,
Kramer K, Hasselwander O (2003) Isomer-specific actions
of conjugated linoleic acid on muscle glucose transport in
the obese Zucker rat. Am J Physiol-Endocrinol Metabol
285(1):E98–E105
180. Sanders SR, Teachey MK, Ptock A, Kraemer K, Hasselwander
O, Henriksen EJ, Baumgard LH (2004) Effects of specific con-
jugated linoleic acid isomers on growth characteristics in obese
Zucker rats. Lipids 39(6):537–543
181. Botelho AP, Santos-Zago LF, de Oliveira AC (2008) Conjugated
linoleic acid supplementation modified the body composition
and serum leptin levels in weaning rats. Arch Latinoam Nutr
58(2):156–163
Lipids
1 3
182. Ogborn MR, Nitschmann E, Goldberg A, Bankovic-Calic
N, Weiler HA, Aukema HM (2008) Dietary conjugated lin-
oleic acid renal benefits and possible toxicity vary with iso-
mer, dose and gender in rat polycystic kidney disease. Lipids
43(9):783–791
183. Roy BD, Bourgeois J, Rodriguez C, Payne E, Young K, Shaugh-
nessy SG, Tarnopolosky MA (2008) Conjugated linoleic acid
prevents growth attenuation induced by corticosteroid adminis-
tration and increases bone mineral content in young rats. Appl
Physiol, Nutr, Metab 33(6):1096–1104
184. DeGuire JR, Weiler HA (2013) Free fatty acid and triacylg-
lycerol forms of CLA isomers are not incorporated equally in
the liver but do not lead to differences in bone density and bio-
markers of bone metabolism. Prostaglandins Leukot Essent Fat
Acids 88(5):399–403
185. de Almeida MM, de Souza YO, Potente Dutra Luquetti SC,
Sabarense CM, do Amaral Correa JO, Santos da Conceicao EP,
Lisboa PC, de Moura EG, Andrade Soares SM, Moura Gual-
berto AC, Gameiro J, Sundfeld da Gama MA, Ferraz Lopes FC,
Gonzalez Garcia RM (2015) Cis-9, trans-11 and trans-10, cis-
12 CLA mixture does not change body composition, induces
insulin resistance and increases serum HDL cholesterol level in
rats. J Oleo Sci 64(5):539–551
186. Berven G, Bye A, Hals O, Blankson H, Fagertun H, Thom E,
Wadstein J, Gudmundsen O (2000) Safety of conjugated lin-
oleic acid (CLA) in overweight or obese human volunteers. Eur
J Lipid Sci Technol 102(7):455–462
187. Riserus U, Arner P, Brismar K, Vessby B (2002) Treatment with
dietary trans10cis12 conjugated linoleic acid causes isomer-
specific insulin resistance in obese men with the metabolic syn-
drome. Diabetes Care 25(9):1516–1521
188. Riserus U, Vessby B, Arnlov J, Basu S (2004) Effects of cis-
9, trans-11 conjugated linoleic acid supplementation on insulin
sensitivity, lipid peroxidation, and proinflammatory markers in
obese men. Am J Clin Nutr 80(2):279–283
189. Larsen TM, Toubro S, Gudmundsen O, Astrup A (2006) Con-
jugated linoleic acid supplementation for 1 y does not prevent
weight or body fat regain. Am J Clin Nutr 83(3):606–612
190. Laso N, Brugué E, Vidal J, Ros E, Arnaiz JA, Carné X, Vidal S,
Mas S, Deulofeu R, Lafuente A (2007) Effects of milk supple-
mentation with conjugated linoleic acid (isomers cis-9, trans-11
and trans-10, cis-12) on body composition and metabolic syn-
drome components. Br J Nutr 98(04):860–867
191. Park E, Kim J, Kim K, Paik H (2008) Conjugated linoleic acid
(CLA) supplementation for 8 weeks reduces body weight in
healthy overweight/obese Korean subjects. Food Sci Biotechnol
17(6):1261–1264
192. Norris LE, Collene AL, Asp ML, Hsu JC, Liu LF, Richardson
JR, Li D, Bell D, Osei K, Jackson RD, Belury MA (2009) Com-
parison of dietary conjugated linoleic acid with safflower oil on
body composition in obese postmenopausal women with type 2
diabetes mellitus. Am J Clin Nutr 90(3):468–476
193. Joseph SV, Jacques H, Plourde M, Mitchell PL, McLeod RS,
Jones PJ (2011) Conjugated linoleic acid supplementation for
8 weeks does not affect body composition, lipid profile, or
safety biomarkers in overweight, hyperlipidemic men. J Nutr
141(7):1286–1291
194. López-Plaza B, Bermejo LM, Weber TK, Parra P, Serra F,
Hernández M, Milla SP, Gómez-Candela C (2013) Effects of
milk supplementation with conjugated linoleic acid on weight
control and body composition in healthy overweight people.
Nutr Hosp 28(6):2090–2098
195. Shadman Z, Taleban FA, Saadat N, Hedayati M (2013) Effect
of conjugated linoleic acid and vitamin E on glycemic control,
body composition, and inflammatory markers in overweight
type2 diabetics. J diabetes metab disord 12(1):1–9
196. Ormsbee MJ, Rawal SR, Baur DA, Kinsey AW, Elam ML,
Spicer MT, Fischer NT, Madzima TA, Thomas DD (2014) The
effects of a multi-ingredient dietary supplement on body com-
position, adipokines, blood lipids, and metabolic health in over-
weight and obese men and women: a randomized controlled
trial. J Int Soc Sports Nutr 11:37
197. Di Felice V, Macaluso F, Montalbano A, Gammazza AM,
Palumbo D, Angelone T, Bellafiore M, Farina F (2007) Effects
of conjugated linoleic acid and endurance training on peripheral
blood and bone marrow of trained mice. J Strength Cond Res
21(1):193–198
198. Banu J, Bhattacharya A, Rahman M, Fernandes G (2008) Bene-
ficial effects of conjugated linoleic acid and exercise on bone of
middle-aged female mice. J Bone Miner Metab 26(5):436–445
199. Zhang G, Shirai N, Higuchi T, Suzuki H, Shimizu E (2009) A
comparative study of the effects of Erabu sea snake (Laticauda
semifasciata) lipids, green tea extract and conjugated linoleic
acid on the swimming endurance of mice. Int J Vitam Nutr Res
79(56):362–374
200. Shen W, Baldwin J, Collins B, Hixson L, Lee K, Herberg T,
Starnes J, Cooney P, Chuang C, Hopkins R, Reid T, Gupta S,
McIntosh M (2015) Low level of trans-10, cis-12 conjugated
linoleic acid decreases adiposity and increases browning inde-
pendent of inflammatory signaling in overweight Sv129 mice. J
Nutr Biochem 26(6):616–625
201. Mirand PP, Arnal-Bagnard MA, Mosoni L, Faulconnier Y,
Chardigny JM, Chilliard Y (2004) Cis-9, trans-11 and trans-
10, cis-12 conjugated linoleic acid isomers do not modify
body composition in adult sedentary or exercised rats. J Nutr
134(9):2263–2269
202. Faulconnier Y, Arnal MA, Mirand PP, Chardigny JM, Chilliard
Y (2004) Isomers of conjugated linoleic acid decrease plasma
lipids and stimulate adipose tissue lipogenesis without chang-
ing adipose weight in post-prandial adult sedentary or trained
Wistar rat. J Nutr Biochem 15(12):741–748
203. Thom E, Wadstein J, Gudmundsen O (2001) Conjugated lin-
oleic acid reduces body fat in healthy exercising humans. J Int
Med Res 29(5):392–396
204. Adams RE, Hsueh A, Alford B, King C, Mo H, Wildman R
(2006) Conjugated linoleic acid supplementation does not
reduce visceral adipose tissue in middle-aged men engaged in a
resistance-training program. J Int Soc Sports Nutr 3(2):28–36
205. Bulut S, Bodur E, Colak R, Turnagol H (2013) Effects of con-
jugated linoleic acid supplementation and exercise on post-hep-
arin lipoprotein lipase, butyrylcholinesterase, blood lipid profile
and glucose metabolism in young men. Chem Biol Interact
203(1):323–329
... Conjugated linoleic acids (CLAs), a group of linoleic acids with conjugated double bonds, have received considerable attention for their potential to regulate energy expenditure, inflammation, and oxidative processes in animals (1,2) . Studies in different animal models have shown that CLA was incorporated into tissues, and modulated lipid metabolism in liver, adipose tissue and muscle (3,4) . CLA, especially the t10c12 isomer, was reported to exert its de-lipidating effects by decreasing fat storage in mature adipocytes and therefore reducing adipocyte size (5,6) , related to the decreased expression of hepatic genes involved in fatty acids synthesis and the increased expression of lipolysis genes (7,8) , or by reducing the differentiation of preadipocytes to mature adipocytes via inhibiting the transcriptional level of adipocyte protein and peroxisome proliferator-activated receptor γ (PPARγ) (9)(10)(11) . ...
... Relative shell mass, shell weight/egg mass.3 Relative yolk mass, yolk sac weight/egg mass.4 ...
Article
This experiment was designed to investigate the effect of supplementing conjugated linoleic acid (CLA) in breeder hens diet on development and hepatic lipid metabolism of chick offspring. Hy-Line Brown breeder hens were allocated into two groups, supplemented with 0 (CT) or 0.5% CLA for 8 weeks. Offspring chicks were grouped according to the mother generation and fed for 7 days. CLA treatment had no significant influence on development, egg quality, and fertility of breeder hens, but darkened the egg yolks in shade and increased yolk sac mass compared to CT group. Addition of CLA resulted in increased body mass and liver mass, and decreased deposition of subcutaneous adipose tissue in chick offspring. The serum triglyceride (TG) and cholesterol (TC) levels of chick offspring were decreased in CLA group. CLA treatment increased the incorporation of both CLA isomers (c9t11 and t10c12) in liver of chick offspring, accompanied by the decreased hepatic TG levels, related to the significant reduction of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) enzyme activities and the increased of carnitine palmitoyltransferase-1 (CPT1) enzyme activity. Meanwhile, CLA treatment reduced the mRNA expression of genes related to fatty acid biosynthesis (FAS, ACC, and sterol regulatory element-binding protein-1c), and induced the expression of genes related to β-oxidative (CPT1, AMP-activated protein kinase, and peroxisome proliferator-activated receptor α) in chick offspring liver. In summary, the addition of CLA in breeder hens diet significantly increased incorporation of CLA in liver of chick offspring, which further regulate hepatic lipid metabolism.
... CLA increases muscle size and promotes muscle hypertrophy, and the hypertrophy may be fiber-type specific. 4,67 However, conflicting results of fiber-type-specific hypertrophy were reported from animal studies. Because of the upregulated oxidative metabolism in skeletal muscles under CLA supplementation, the formation of slow oxidative type I fiber was promoted in mice 1 and pigs. ...
Article
Context Conjugated linoleic acid (CLA) has been reported to have anti-obesity and antidiabetic effects. However, the benefits of CLA combined with exercise remain unclear, and studies report conflicting results. Objective A systematic review and meta-analysis were performed to investigate the synergistic effect of CLA and exercise on body composition, exercise-related indices, insulin resistance, and lipid profiles; and of the safety of CLA supplements. Data sources In October 2021, the PubMed, Embase, and Cochrane Library databases were searched for reports on clinical trials of the combined intervention of CLA and exercise. Data extraction A total of 18 randomized controlled trials and 2 crossover trials were included. The methodological quality assessment was performed using the revised Cochrane risk-of-bias tool. Pooled effect sizes were reported as standardized mean difference (SMD) for continuous data and risk ratio for dichotomous data with their corresponding 95% confidence intervals (CIs). Heterogeneity was tested using the I2 statistic. Data analysis The combination of CLA and exercise resulted in significantly decreased body fat (SMD, –0.42 [95%CI, –0.70, –0.14]; P = 0.003; I2 = 65) and insulin resistance (SMD, –0.25 [95%CI, –0.44, –0.06]; P = 0.01; I2 = 0) than did exercise alone. In subgroup analysis, the following factors were associated with significant outcomes: (1) body mass index ≥25 kg/m2; (2) female sex; (3) follow-up time >4 weeks; and (4) intervention duration >4 weeks. Nevertheless, supplementation with CLA during exercise programs was not effective for body-weight control, exercise performance enhancement, or lipid-profile improvement. CLA in combination with exercise did not result in a higher risk of adverse events (risk ratio, 1.32 [95%CI, 0.94–1.84]; P > 0.05; I2 = 0). Conclusion CLA combined with exercise is generally safe and can lower body fat and insulin resistance but does not reduce body weight, enhance exercise performance, or improve lipid profiles.
... It is an ideal nutritional meat for patients with hypertension and cardiovascular disease (Dalle Zotte and Szendro 2011). Conjugated linoleic acid (CLA) is a mixture of several geometric and positionally conjugated isomers of linoleic acid and has received considerable attention for its potential to regulate fat metabolism, reduce cholesterol, inhibit atherosclerosis, improve immunity, improve bone density, prevent diabetes and promote growth in animals (Shen et al. 2013;Kim et al. 2016;Shen and McIntosh 2016;Chen et al. 2019). In addition, supplementing CLA in poultry diets has been suggested as a way to obtain CLA-enriched meat and egg products (Aydin and Cook 2009;Kumari et al. 2014). ...
Article
Full-text available
This experiment was conducted to study the effects of dietary conjugated linoleic acids (CLAs) on the growth performance, fat metabolism, carcase composition and muscle quality of fattening rabbits. A total of 160 Minxinan black rabbits aged 75 days with body weights of 1658.9 ± 188.8 g were randomly divided into 4 groups. They were fed a basic diet supplemented with 0 (control), 0.5%, 1.0%, or 1.5% CLA for 50 days. Dietary CLA reduced the feed intake and serum triglyceride and cholesterol levels. In addition, the crude protein content in rabbit meat was increased, along with the cholesterol and the ether extract levels in the 1.5% depression group. Moreover, the fatty acid composition in rabbit meat was changed, and the content of polyunsaturated fatty acids/monounsaturated fatty acids (PUFAs/MUFAs) increased with the increasing levels of CLA addition. These findings indicate that CLA greatly improved the nutritional value of rabbit meat. From an economic point of view, CLA would normally be included at a concentration of 0.5% in the formulation of feeds for fattening rabbits. • HIGHLIGHTS • Minxinan black rabbits were fed conjugated linoleic acid (CLA)- supplemented diets for 50 d. • CLA decreased the feed intake of experimental rabbits. • CLA has significant effects on fat deposition and serum triglyceride and cholesterol levels. • CLA greatly improved the nutritional value of rabbit meat. • The recommended CLA level is 0.5% for meat rabbits.
... CLA, among all, are important for athlete general health [22]. Kim et al. [101] reviewed the impact of CLA on muscle metabolism, specifically observed, in several animal trials, an improvement in the exercise outcome with CLA treatment, however, human studies are still limited and require further investigation. ...
Article
Full-text available
Physical activity (PA) and sport play an essential role in promoting body development and maintaining optimal health status both in the short and long term. Despite the benefits, a long-lasting heavy training can promote several detrimental physiological changes, including transitory immune system malfunction, increased inflammation, and oxidative stress, which manifest as exercise-induced muscle damages (EIMDs). Meat and derived products represent a very good source of bioactive molecules such as proteins, lipids, amino acids, vitamins, and minerals. Bioactive molecules represent dietary compounds that can interact with one or more components of live tissue, resulting in a wide range of possible health consequences such as immune-modulating, antihypertensive, antimicrobial, and antioxidative activities. The health benefits of meat have been well established and have been extensively reviewed elsewhere, although a growing number of studies found a significant positive effect of meat molecules on exercise performance and recovery of muscle function. Based on the limited research, meat could be an effective post-exercise food that results in favorable muscle protein synthesis and metabolic performance.
... The decrease of milk fat caused by t10c12-CLA can be alleviated by adding palmitic acid (62). At the cellular level, 150 mol/L t10c12-CLA treatment of BMECs for 48 h significantly reduced MCFA and unsaturated fatty acid (USFA) content by 17.1 and 26.5%, respectively, and mRNA abundance of FASN and ACACA (63), this negative regulatory effect was accomplished in part by inhibiting SREBP1 activity (64) or activating the AMPK signaling pathway (65). This result was further confirmed by Zhang et al. (66). ...
Article
Full-text available
Milk fat is the most important and energy-rich substance in milk and plays an important role in the metabolism of nutrients during human growth and development. It is mainly used in the production of butter and yogurt. Milk fat not only affects the flavor and nutritional value of milk, but also is the main target trait of ruminant breeding. There are many key genes involve in ruminant milk fat synthesis, including ACSS2, FASN, ACACA, CD36, ACSL, SLC27A, FABP3, SCD, GPAM, AGPAT, LPIN, DGAT1, PLIN2, XDH, and BTN1A1. Taking the de novo synthesis of fatty acids (FA) and intaking of long-chain fatty acids (LCFA) in blood to the end of lipid droplet secretion as the mainline, this manuscript elucidates the complex regulation model of key genes in mammary epithelial cells (MECs) in ruminant milk fat synthesis, and constructs the whole regulatory network of milk fat synthesis, to provide valuable theoretical basis and research ideas for the study of milk fat regulation mechanism of ruminants.
... Because of integrated spermatin patients with MBH carbonate hormone (TH) energy metabolism, there is a disorder such as brain metabolism. In the cerebral metabolism analysis of obese adolescents, the collected water-soluble model compound Na-model underwent asymmetric Michael experiment to obtain an obese adolescent cerebral metabolism to decompose the physiological response process [13,14]. It can be seen from the reaction process that adolescent obesity is a chronic metabolic disease, and the fat abnormality of the physiological response process of brain metabolism is increased, resulting in endocrine disorders. ...
Article
Full-text available
In order to enable obese adolescents to increase muscle content, base metabolism, etc., aerobic training is used reduce body fat and then improve body components, health physique indicators, and physical fitness. This paper adopts the current situation for research and model construction through the K-center algorithm. The results show that 10 min swimming movement increased the adolescent patients’ level of brain metabolism, and with no less than 15 min, the CI value rose to 41, the increase in brain metabolism in adolescents, and the rate of fat combustion effectively increased. It is guaranteed that physical health prevents the occurrence of obese syndrome diseases. Sports training can not only increase the skinny weight of the teen obese population but also reduce body fat content, which has a significant assistance to body type, is a high-cost performance, and has comprehensive training means.
... (See more on pre-and probiotics in the Microbiome section.) The implications of long-chain polyunsaturated fatty acids (e.g., conjugated linoleic acid, alpha-linolenic acid, and omega-3 fatty acids) as functional foods have also been studied, showing various benefits on bone, muscle and fat tissues [40,41,81]. However, as far as lean and adipose tissue, most investigations have been performed using supplements for muscle enhancement and/or weight loss and they will not be discussed here. ...
Article
Full-text available
As more insight is gained into personalized health care, the importance of personalized nutritional and behavioral approaches is even more relevant in the COVID-19 era, in addition to the need for further elucidation regarding several diseases/conditions. One of these concerning body composition (in this context; bone, lean and adipose tissue) is osteosarcopenic adiposity (OSA) syndrome. OSA occurs most often with aging, but also in cases of some chronic diseases and is exacerbated with the presence of low-grade chronic inflammation (LGCI). OSA has been associated with poor nutrition, metabolic disorders and diminished functional abilities. This paper addresses various influences on OSA and LGCI, as well as their mutual action on each other, and provides nutritional and behavioral approaches which could be personalized to help with either preventing or managing OSA and LGCI in general, and specifically in the time of the COVID-19 pandemic. Addressed in more detail are nutritional recommendations for and roles of macro- and micronutrients and bioactive food components; the microbiome; and optimal physical activity regimens. Other issues, such as food insecurity and nutritional inadequacy, circadian misalignment and shift workers are addressed as well. Since there is still a lack of longer-term primary studies in COVID-19 patients (either acute or recovered) and interventions for OSA improvement, this discussion is based on the existing knowledge, scientific hypotheses and observations derived from similar conditions or studies just being published at the time of this writing.
Article
Conjugated linoleic acid (CLA) is a potential nutritional strategy to regulate meat quality in pigs and produce high-quality pork. However, the effects of CLA on nutritional quality, lipid dynamics, microbiota, and their metabolites in the gut of pigs remain unclear. Our study explored the effects of CLA on lipo-nutritional quality based on a Heigai pig model and investigated the regulatory mechanism using an integrated analysis of multiple omics. A total of 58 Heigai finishing pigs (body weight: 85.58 ± 10.39 kg) were randomly divided into 2 treatments and fed diets containing 1% soyabean oil and 1% CLA for 40 days. 1% CLA significantly decreased the backfat thickness (P < 0.05) and increased the intramuscular fat (IMF) content (P < 0.05). The expression of lipid metabolism-related genes was significantly changed (P < 0.05) and lipidome analysis showed the alternations of lipid dynamics in the longissimus dorsi muscle (LDM). In addition, based on the microbiome and metabolomic analyses, the relative abundances of Parabacteroides, Bacteroides, and Lachnospiraceae_UCG-010 increased and CLA changed the metabolome profiles and the short-chain fatty acid (SCFA) composition in the gut, which were significantly increased (P < 0.05). Additionally, Pearson's correlation analysis indicated that differential microbial genera and SCFAs induced by CLA had tight correlations with the backfat thickness, IMF content and lipids in the LDM. CLA enhances the lipid accumulation and metabolism in muscle and these changes are associated with the production and functions of the differential bacteria and SCFAs in the gut of pigs.
Article
Full-text available
Introducción: La grasa es uno de los macronutrientes de la leche entera de vaca (LEV) más controversiales por su papel en el desarrollo de la obesidad y sobrepeso. Sin embargo, existe suficiente evidencia que contradice que la leche entera de vaca tenga responsabilidad en el desarrollo de obesidad o sobrepeso. El objetivo de este estudio fue evaluar el efecto de LEV dentro de una intervención dietética para la pérdida de masa grasa en adultos con obesidad o sobrepeso. Metodología: Estudio semi experimental, no aleatorio, con diseño paralelo de 40 pacientes a quienes se les prescribió el mismo esquema de dietoterapia, diferenciado por el tipo de leche que habitualmente consumían; 10 por cada tipo de leche: entera (LE), semidescremada (LS), descremada (LD), sin leche (SL). Cada sujeto fue evaluado durante tres meses. Se comparó la pérdida de kilos de grasa entre los 4 grupos. Resultados: La probabilidad de perder 4 kg de grasa para LE fue 20 veces mayor que para SL (OR = 21), cinco veces mayor que para LD (OR = 6), y ocho veces mayor que para LS (OR = 9). No se encontraron diferencias significativas al comparar la actividad física basal y final (p = 0.197). Conclusiones: Este estudio arrojó evidencia de que las personas que consumen LE registran mayor pérdida de grasa que quienes consumen otro tipo de leche o que no consumen leche, independientemente de la actividad física.
Article
Full-text available
Ergojenik destek, biyolojik enerji kullanımını ve üretimini arttıran, egzersiz performansını olumlu yönde etkileyen, hastalık oluşumu ve yaralanmaları önleyen ve stresle baş etmeyi sağlayan maddeler, araçlar ve uygulamalardır. Başka bir deyişle ergojenik destek; sporcuların performans kapasitesini ve çalışma verimini arttıran, egzersizlerden sonra çabuk toparlanmayı sağlayan uygulama ya da tekniklerdir. Sporcuların beslenmesi ve ergojenik destek kullanımı her geçen gün popülerliği artan konulardandır. Çeşitli ergojenik destek ürünleri olsa da en çok bilinen formu besinsel desteklerdir. Sporcular tarafından performansı geliştirmek için kullanılan özel diyetler ve beslenme uygulamaları, besinsel ergojenik desteklerdir. Bunların kullanımı da son on yılda önemli ölçüde artmıştır. Besinsel sporcu desteklerinin öncelikli amacı, performansın artmasını sağlamak, vücut yağ oranını dengelemek ve protein sentezlenmesini aktif hale getirmektir. Ergojenik destekler de kuvveti, dayanıklılığı, hızı ve beceriyi sürekli olarak arttırmaya yönelik kullanılırlar. Egzersiz öncesi ve sırasında alınan besinsel desteklerin ise vücut depolarını yeniden doldurduğu, sıvı dengesini sağladığı ve müsabakalar arasında toparlanmayı kolaylaştırdığı bu nedenle de sportif açıdan avantaj sağladığı düşünülmektedir. Tüm bu yaklaşımlar sonucunda sporcu besin destek ürünlerinin performans arttırmada yararlarının olduğu görülmektedir. Ancak doğru ürün, doğru zamanda, doğru miktarda ve profesyonel yardım ile alındığında performans artışı sağlayabilir. Doğru destek ürünlerinin kullanılmadığı durumlarda sporcularda görülecek fayda düşebilir ya da hiç fayda görmezler. Bu derleme spor dünyasında sıklıkla kullanılan ve performans üzerinde çeşitli etkileri olan ergojenik destek ürünlerinin yapısını, sportif performansa etkilerini ve önerilen kullanım miktarlarını güncel alan literatür çerçevesinde incelenmesini amaçlamaktadır.
Article
Full-text available
Several dietary supplements used for weight loss have been reported to cause hepatotoxicity. Conjugated Linoleic Acid (CLA) is a dietary supplement that has been shown to cause reduction in body fat mass. Here, we present the first case of CLA induced acute hepatitis in the United States and only the third case in the worldwide literature along with a brief review of the literature.
Article
Full-text available
Conjugated linoleic acid (CLA) has been reported to prevent body weight gain and fat accumulation in part by improving physical activity in mice. However, the effects of post-weaning administration of CLA on development of obesity later in life have not yet been demonstrated. The current study investigated the role of post-weaning CLA treatment on skeletal muscle energy metabolism in genetically induced inactive adult-onset obese model, nescient basic helix-loop-helix 2 knock-out (N2KO) mice. 4-week-old male N2KO and wild type mice were fed either control or CLA containing diet (0.5%) for 4-weeks and then CLA was withdrawn and control diet provided to all mice for the following 8-weeks. Post-weaning CLA supplementation in wild type animals, but not N2KO mice, may activate AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-δ (PPARδ) as well as promote desensitization of phosphatase and tensin homolog (PTEN) and sensitization of protein kinase B (AKT) at threonine 308 in gastrocnemius skeletal muscle, improving voluntary activity and glucose homeostasis. We suggest that post-weaning administration of CLA may in part stimulate the underlying molecular targets involved in muscle energy metabolism to reduce weight gain in normal animals, but not in the genetically induced inactive adult-onset animal model.
Article
Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in the fat of beef and other ruminants. CLA is reported to have effects on both tumor development and body fat in animal models. To further characterize the metabolic effects of CLA, male AKR/J mice were fed a high-fat (45 kcal%) or low-fat (15 kcal%) diet with or without CLA (2.46 mg/kcal; 1.2 and 1.0% by weight in high- and low-fat diets, respectively) for 6 wk. CLA. significantly reduced energy intake, growth rate, adipose depot weight, and carcass lipid and protein content independent of diet composition. Overall, the reduction of adipose depot weight ranged from 43 to 88%, with the retroperitoneal depot most sensitive to CLA. CLA significantly increased metabolic rate and decreased the nighttime respiratory quotient. These findings demonstrate that CLA reduces body fat by several mechanisms, including a reduced energy intake, increased metabolic rate, and a shift in the nocturnal fuel mix.
Article
In the present study, a randomized, double-blind, placebo-controlled trial to determine the effect of conjugated linoleic acid (CLA) supplementation (50:50 ratio of cis-9, trans-11 and trans-10, cis-12 isomers) for 8 weeks on body composition and biochemical parameters in healthy overweight/obese (body mass index, BMI≥23 kg/m2) Korean subjects was performed. Thirty participants (3 males and 27 females) were randomized to receive placebo (2.4 g olive oil/day) or 2.4 g/day CLA (mixture containing 36.9% of cis-9, trans-11 and 37.9% of trans-10, cis-12). Eight weeks of CLA supplementation significantly decreased body weight by -0.75 kg, BMI by -0.27 kg/m2, and hip circumference by -1.11 cm. The reduction of body weight was ascribed to the reduction of body fat mass (-0.59 kg) and lean body mass (-0.18 kg), although these changes were not significant. No significant differences in serum lipid profiles, liver function enzyme activities, and protein concentration were observed in either the CLA or placebo groups. These results indicate that short term supplementation (8 weeks) with CLA (2.4 g/day) may decrease body weight in Korean overweight/obese subjects.
Chapter
Skeletal muscle is unique because in addition to its aerobic capacity, it is adapted for short-term anaerobic activity, allowing for both extended physical activity of a lower intensity and short-term high-energy output. The dynamic range for the change in rate of ATP utilization is large, in excess of 100-fold for skeletal muscle. Changes in ATP use require compensatory adjustments of circulatory, cardiac and respiratory functions. In humans at rest, skeletal muscle receives about 5 ml blood/100 g tissue. During heavy exercise the share of cardiac output of the muscle tissue can increase in trained subjects up to 80% of the total cardiac output or even more (Fig. 1). The extraction of the oxygen also increases, as evidenced by the increasing arteriovenous difference from 25% at rest to 80% or even more in maximal exercise. Thus, oxygen consumption in exercising human muscle can increase about a hundredfold, which is in fact quite modest in comparison to some animals, in which the increase can be a thousandfold.
Article
Since conjugated linoleic acid (CLA) was identified as an anticancer component from beef extract, it has shown other beneficial bioactivities. Among them, the most interesting aspect of CLA is its ability to control body fat levels. The chapter reviews the current knowledge of CLA supplementation in humans, with a particular focus on its effects on weight and body fat control. The suggested mechanisms of CLA with regard to body fat regulation, as well as considerations of age, study design, interaction between CLA and exercise and other dietary supplementations are discussed, and data from animal and human studies are compared. Other human health benefits of CLA (cancer prevention, cardiovascular diseases, immune and inflammatory responses, and bone health) are reviewed. Potential adverse effects associated with CLA supplementation, such as its role in oxidative stress, glucose metabolism, milk fat depression, and liver functions, are also discussed.
Article
This study investigated the effect of conjugated linoleic acid (CLA) on the aerobic capacity and anthropometric measurements of humans. Although this effect has been shown in animal studies, human studies have reported controversial results. In this double-blind, placebo-controlled, randomized clinical trial, 80 non-trained healthy young men received a 50:50 mixture of cis-9,trans-11 and trans-10 cis-12 CLA (CLA 4 × 0.8 g day(-1)) ora placebo (PLA; soybean oil) in an 8-week intervention. Maximal oxygen consumption (VO2 max), time to exhaustion, weight, body mass index (BMI) and waist circumference (WC) were measured. CLA had no effect on VO2 max (p = 0.5) also no change was seen in time to exhaustion (p = 0.51), weight (p = 0.7), BMI (p = 0.7) and WC (p = 0.8) vs PLA. Our results suggest that CLA has no significant effect on VO2 max, time to exhaustion and anthropometric measurements in untrained healthy young male students.