This article from "Journal of the American Dietetic Association
Volume 104, Issue 6 , June 2004, Pages 963-968" might help you.
Research: review
Conjugated linoleic acid:next term health implications and effects on
body composition
Lisa Rainer MS, RDCorresponding Author Contact Information, E-mail The
Corresponding Author and Cynthia J. Heiss PhD, RD
Abstract
previous termConjugated linoleic acidnext term (CLA) is attracting
interest because of its purported effects on body composition,
specifically a reduction in body fat mass and an increase in lean body
mass. Other reported beneficial health-related effects of CLA include
anticarcinogenic, antiatherogenic, antidiabetogenic, and immune
modulating properties. Because research on CLA has been almost
exclusively in animals and the mechanism(s) by which CLA exerts its
effects remain largely unknown, scientists are extremely cautious
about making definitive statements about CLA. Despite the limited
research on CLA in human subjects, numerous Internet websites and
health food stores sell CLA supplements or CLA-containing products as
weight loss or ergogenic aids. The increasing popularity of CLA as a
dietary supplement makes it important that dietitians and health
professionals are aware of CLA and are able to provide the public with
science-based information regarding CLA.
The increased interest in conjugated linoleic acid (CLA) is the result
of numerous animal studies associating CLA with beneficial health
properties such as reducing the risk for cancer (reviewed in [1]),
atherosclerosis [2 and 3], and diabetes [4]. CLA has also been shown
to have positive effects on immune function [5 and 6] and body
composition. Despite the numerous health benefits seen in CLA-fed
animals, the health effects of CLA in human beings remain
controversial. As a result of the limited research using human
subjects, most scientists remain cautious about making definitive
statements about the benefits of CLA in human health.
The reported effects of CLA on body composition, specifically a
reduction in body fat mass and an increase in lean body mass [7 and
8], are generating interest among health professionals, athletes, and
dietary supplement manufacturers. Numerous Internet websites and
health food stores sell CLA supplements or CLA-containing products as
weight loss or ergogenic aids. Moreover, several websites claim to
sell CLA supplements that contain the exact isomers that are reported
to have the greatest levels of protection against disease and previous
termobesity.next term This article discusses CLA and its purported
health benefits, describes various studies on the effects of CLA on
body composition in animals and human beings, and addresses safety
issues regarding supplementation.
CLA defined
CLA is a descriptor for all positional and geometric conjugated
dieonic isomers of linoleic acid [9]. Linoleic acid, or cis-9 and
cis-12 octadecadienoic acid, is an 18-carbon fatty acid containing two
double bonds in positions 9 and 12. Linoleic acid can be converted to
CLA when a microbial or chemical reaction shifts the double bonds to
form alternating double and single bonds, hence the term conjugated
linoleic acid [9 and 10]. The double bonds of a CLA may be in
positions 7,9; 8,10; 9,11; 10,12; or 11,13 along the chain of 18
carbons. The two isomers known to possess biological activity are
cis-9, trans-11 and trans-10, cis-12 [11].
Sources of CLA
Biological synthesis of CLA occurs through the microbial isomerization
of dietary linoleic acid in the digestive tracts of ruminant animals
(reviewed in [11]). Therefore, ruminant species and their products are
rich dietary sources of CLA (Table), which is ironic in that animal
fats have long been criticized as promoters of chronic disease.
However, because CLA is a fatty acid, the making of "fat free" and
"reduced fat" dairy products results in decreased amounts of this
compound in foods. CLA isomers can also be commercially produced by
heating linoleic acid in the presence of alkali or by partial
hydrogenation of linoleic acid [10].
Table. Conjugated linoleic acid content of various foodsa, b
Full Size Table
Several factors influence the CLA content of food products, such as
temperature, protein quality, choice of starter cultures, and period
of aging (reviewed in [12]). Variations of CLA content in foods are
also affected by the animal?s diet (type of feed, feeding regimen,
grass quantity, dietary restriction), animal age or breed, and
seasonal factors (reviewed in [12]). Other processing factors that can
influence the CLA content in dairy and meat products include cooking
methods (grilling), the addition of hydrogen donors (butylated
hydroxytoluene, propyl gallate, or ascorbic acid), and the addition of
whey protein (reviewed in [13]). CLA in beef reportedly increases with
grilling [14]; however, a subsequent study found no effect of cooking
on the CLA concentration in beef [15]. CLA was found to remain stable
in the processes of cooking and storage [15].
The seasonal variation of CLA is significant, with the highest levels
in cow?s milk reported during the summer months when the cows are
allowed to graze in pastures (reviewed in [16]). When cows are allowed
to graze freely in pastures, their milk contains substantially higher
CLA compared with the milk from cows that are confined and fed grain
concentrates (reviewed in [13 and 16]). CLA concentrations in milk are
twofold to threefold higher in Australia and New Zealand, where cows
graze freely, as compared with the reported values from cows in North
America and Northern Europe (reviewed in [12 and 16]).
Health implications of CLA
Most of the research on CLA is associated with its anticarcinogenic
properties. CLA was first identified as having anticarcinogenic
properties in 1987, when researchers announced that they had
identified an agent (produced by alkaline isomerization of linoleic
acid) in grilled beef that inhibited cancer in the epidermis of mice
[14]. Both the cis-9, trans-11 and trans-10, cis-12 CLA isomers have
been recognized as having antitumor capabilities in the inhibition of
angiogenesis in mammary tissues [17].
CLA reportedly has anticarcinogenic effects at various stages of
cancer development, including initiation, progression, and metastasis
(reviewed in [1 and 17]). Studies have shown that CLA can delay or
reduce the onset of chemically induced tumors in various sites of rats
and mice, including skin, mammary glands, and forestomach [14, 18, 19,
20, 21 and 22]. Proposed mechanisms of CLA and its anticarcinogenic
activities include a reduction in cell proliferation [21], vitamin A
metabolism [23 and 24], and prostaglandin metabolism [25]. CLA seems
to significantly reduce prostaglandin E2 synthesis in the mouse
epidermis, which could inhibit tumor formation [26].
CLA may impact the immune system. In animals, it is reported that CLA
serves as a protection from the catabolic effects of immune
stimulation [5 and 6]. CLA seems to have a protective effect against
the catabolism and inflammatory responses induced by cytokines,
specifically tumor necrosis factor-? (TNF-?) [9 and 25]. A diet
supplemented with 0.5% CLA had protective effects against
TNF-?-induced cachexia [25].
CLA supplementation has been shown to exert various responses on
lipidemic profiles. Feeding rabbits an atherogenic diet supplemented
with CLA (0.5 g CLA/rabbit/day) resulted in a reduction of
atherogenesis in lipid deposition and in connective tissue development
[2]. By the 12th week, the CLA-fed rabbits displayed reduced aortic
plaque formation and a decrease in total cholesterol, low-density
lipoprotein cholesterol, and triglycerides [2]. Similarly, hamsters
fed a hypercholesterolemic diet supplemented with CLA (1% of the diet)
showed reduced aortic plaque formation [3]. In contrast, studies using
rat and pig models have shown no effect of dietary CLA on serum lipids
[16]. One of the possible mechanisms for the antiatherogenic
properties of CLA in animal models is by the reduction of
apolipoprotein-B secretion [27].
CLA is reported to have antidiabetic effects in rats, including
improved insulin sensitivity [4]. In human beings, supplementation
with mixed isomers of CLA was associated with improved fasting blood
glucose [28]. Conversely, supplemental CLA actually increased insulin
resistance in mice [29] and in obese men with metabolic syndrome [30].
The trans-10, cis-12 CLA isomer, not a CLA mixture, was responsible
for the increased insulin resistance, fasting blood glucose levels,
and dyslipidemia [30]. The reported mechanisms for this isomer
inducing insulin resistance is through increased oxidative stress [31]
or the increased lipolytic rate and free fatty acid levels associated
with supplementation [7]. The oxidant property of the trans-10, cis-12
CLA isomer may heighten the risk for cardiovascular disease, which
warrants further investigation.
CLA and lipid metabolism
Various studies have shown that CLA affects lipid metabolism. In
lactating cows, the trans-10, cis-12 CLA isomer resulted in a 42%
reduction of milk fat synthesis and a 44% reduction in the yield of
milk fat [32]. The mechanism for the reduction in milk fat synthesis
by CLA is unknown.
In human adipose tissue, the trans-10, cis-12 isomer of CLA decreased
the triacylglyceride content and glucose incorporation into stromal
vascular cells [33]. Another study with human subjects showed that
supplementation with 3.0 g/day of mixed isomers of CLA (50% cis-9,
trans-11 and 50% trans-10, cis-12) significantly reduced fasting
plasma triacylglycerol concentrations [34]. In the same study, the 80%
cis-9, trans-11 and 20% trans-10, cis-12 CLA supplement significantly
reduced very low density lipoprotein cholesterol concentrations. The
ability of CLA to alter lipid metabolism may involve such factors as
its ability to induce apoptosis [29, 35 and 36], increase rates of
lipolysis and fatty acid oxidation, and reduce tissue uptake of fatty
acids [34].
CLA and body composition
Several animal studies have shown the ability of CLA to reduce
adiposity and increase lean body mass [4, 7, 8, 37, 38, 39 and 40].
The body composition changes seen in mice are associated with the
trans-10, cis-12 CLA isomer [25]. Several hypotheses have evolved to
explain the CLA-induced changes in body composition.
CLA was first reported to influence body composition in a study with
mice that were fed 0.5% CLA (50% cis-9, trans-11 and 50% trans-10,
cis-12), resulting in a decreased body fat mass and an increased lean
body mass [8]. The investigators speculate that these effects may be
the result of increased lipolysis, increased fatty acid oxidation (as
evidenced by increased carnitine palmitoyltransferase activity), or
reduced fatty acid uptake in adipocytes [8]. Another study found that
CLA did not increase lipolysis in mice but rather affected fat
metabolism at an earlier stage, such as reduced fat deposition [41].
In this study CLA also reduced glucose metabolism and lipogenesis but
had no effect on body weight [41].
It has been observed that feeding 4-week-old rats a CLA-supplemented
diet results in a 42% reduction of serum leptin concentration, a
reduction of body fat mass, and a 5.2% decrease in body weight [42].
In this study, CLA enhanced carnitine palmitoyltransferase (CPT)
activity in certain tissues, indicating a greater efficiency of fatty
acid oxidation. A higher CPT level may be associated with inhibition
of triglyceride storage in adipose tissue, resulting in decreased fat
accumulation.
It is reported that a reduction in the body fat of CLA-fed mice occurs
regardless of diet composition. CLA-treated mice fed either a high-fat
(45%) or a low-fat (15%) diet for 6 weeks showed significantly reduced
growth rates, energy intake, adipose depot weight, and carcass lipid
and protein content compared with the non-CLA treated mice controls
[37]. The hypothesized mechanisms for the reduction of body fat were a
reduced energy intake, an increased metabolic rate, or a shift in the
nocturnal fuel mix. The investigators speculated that the CLA-induced
increased energy expenditure could be from the heightened activity of
the autonomic nervous system, a direct action on metabolism in
specific tissues or organs, or the ability to alter energy
utilization/availability through such activities as increased
lipolysis.
Mice fed a high-fat diet with a 1% (1 g/100 g) admixture of CLA
isomers for 5 weeks showed a rapid decrease in fat stores but showed
no change in body weight or energy intake [39]. The investigators
reported that the reduced fat mass was found not to be the result of
reduced de novo synthesis of fatty acids but rather a mechanism
related to increased energy expenditure. The increased energy
expenditure may be the result of an elevated basal metabolic rate, the
enhanced thermal effect of food, or an increase in physical activity.
Feeding rats 0.25% to 0.5% of a mixture of CLA isomers for 5 weeks
reduced retroperitoneal and parametrial fat pad weights without
affecting growth rate or food intake [40]. The reduction in fat mass
is reported to be the effect of decreased lipid deposition and
increased lipolysis [40]. CLA supplementation may be species and
gender dependent, because reductions in fat mass were seen only in
11-week-old female pups, but not in males [43]. Both of these studies
showed that the reduced fat mass was attributable to the reduction in
cell size rather than a reduction in cell number [40 and 43].
There is evidence that the CLA-induced reduction of body fat is dose
dependent. This was demonstrated when mice treated with different
amounts of CLA (0.25% to 1.0%) showed a rapid decrease in fat
accumulation, as well as an increase in protein accumulation in
correlation with the dose of CLA, without altering their food intake
[7]. The mechanism for the increased protein accumulation is unknown.
The decreased fat accumulation was independent of energy intake. Later
studies have reinforced the conclusion that the reduction in body fat
is not related to energy intake [38 and 39].
The effects of CLA on body composition may be limited to growing lean
animals. Feeding lean and obese rats diets containing either 0 or 0.5%
CLA for 5 weeks induced a reduction in the fat mass of growing rats,
but not in rats with established previous termobesitynext term [44].
At the end of the experiment, the obese genotype was significantly
heavier and had elevated insulin, triglycerides, and urea nitrogen
levels.
Despite the evidence that CLA induces changes in body composition in
animals, studies using human subjects are limited and contradictory. A
94-day study using 17 women, ages 20 to 41 years, supplemented with
3.0 g/day of mixed CLA isomers indicated no significant effect on body
composition or energy expenditure with either CLA or placebo capsules
[45]. From the previous study, a subset of six women was chosen to
examine the effects of CLA supplementation (3.9 g/day) on fatty acid
and glycerol kinetics. Four weeks of daily CLA supplementation in
healthy adult women showed no significant effects on lipolytic rates,
free fatty acid release by lipolysis, or free fatty acid
re-esterification rates [46].
In contrast, a reduction in body fat mass was seen among overweight
and obese male and female volunteers supplemented with either 3.4
g/day or 6.8 g/day of CLA mixed isomers (50% cis-9, trans-11 and 50%
trans-10, cis-12) [47]. It was also reported that the 6.8 g/day CLA
supplemented group showed increased lean body mass, however, this
group also had a significant increase in the amount of intensive
training during the study. Thus the reduced fat mass and increased
lean mass may have been enhanced by the increase in training rather
than by CLA. Another study involving nonobese young men and women
supplemented with 0.7 to 1.4 g CLA daily for 4 to 8 weeks resulted in
a decrease in body fat and fat mass [48].
The effects of CLA on body composition entice athletes, especially
bodybuilders, to use supplemental CLA as an ergogenic aid. One study
examined the effect of CLA on mitigating muscle proteolysis, muscle
fiber breakdown (creatine kinase), and cortisol and found no
significant changes in the measured parameters with CLA
supplementation [48]. Similarly, another study indicated that CLA does
not seem to exert any ergogenic activity in 23 experienced,
resistance-trained athletes [49]. The American Dietetic Association
recommends that athletes avoid the use of nutritional ergogenic aids
until the product has been carefully evaluated and the use of the
product has been discussed with a qualified nutrition or health
professional [50].
Safety of CLA supplementation
Despite the numerous health benefits associated with CLA, there are
reports of adverse health effects. A study of CLA supplementation in
mice, resulting in a reduction of fat mass by adipocyte apoptosis,
caused insulin resistance and marked hepatomegaly characteristic of
lipodystrophy [29]. The investigators speculate that a leptin
deficiency may explain the insulin resistance because leptin functions
to normalize blood insulin concentrations and reduce fat deposition in
the liver [29]. Other studies have reported similar effects of CLA
supplementation and increased liver and spleen weight in rats [7 and
37] and insulin resistance [7 and 30]. The reports of adverse effects
in human subjects are limited, with the most common being of
gastrointestinal origin [47 and 51].
A dose of 3.4 g/day of CLA was well tolerated and was reported as a
safe dose in healthy human populations with regard to the safety
parameters investigated [51]. Safety was measured by analysis of blood
samples and registration of adverse events together with a clinical
examination before and after the treatment [51]. The potential for
people to attempt to increase their CLA intake through dietary
measures (ie, increasing fatty food consumption) is ill-advised
because the research of CLA in human beings is inconclusive and high
fat intakes are associated with adverse health effects.
Limitations of CLA studies
Confounding variables in the CLA studies that involved free-living
human subjects included the subjects? diets and activity levels. In
some instances, no explanation was provided on how the diet and
activity levels were controlled. In other cases, food records were
used, which involves errors in the accuracy of reporting and the
reliability of instruments used to analyze the food records. The
placebo effect can also influence the outcomes of a study.
Many studies were performed using a mixture of CLA isomers, as opposed
to an isolated isomer. Researchers use mixed isomers because isolating
each isomer of CLA commercially produced from vegetable oil is a
difficult and expensive process. The disadvantage of using mixtures of
CLA isomers is that it becomes difficult to explain the effects or
mechanisms of CLA without knowing which isomer(s) initiated the
effect. This is important because different isomers assert different
activities and mechanisms of action on specific tissues and organs.
For example, the cis-9, trans-11 isomer is associated with the
anticarcinogenic properties of CLA and the trans-10, cis-12 isomer is
associated with the effects of lipid metabolism and body composition
[11].
CLA dosage and length of feeding time in animal and human studies vary
from study to study. CLA dosages used in animal studies greatly exceed
the dosages used in human studies. These variables make it difficult
to generalize the results to human beings.
Conclusions
CLA, a term used for the conjugated isomers of linoleic acid, is a
group of naturally occurring trans-fatty acids found in foods from
ruminant animal sources [52]. It is important that dietetics
professionals are able to provide the public with science-based
information regarding CLA because of its proposed health benefits
along with its increasing use as a dietary supplement. This group of
naturally occurring trans fats should not be associated with the
notorious effects of the man-made trans fats found in most snack foods
[52].
Although there is evidence that CLA exerts positive health effects in
animals, there is little scientific information on its effects in
human beings, making it difficult to predict the long-term effects of
CLA supplementation. Furthermore, the existing studies of CLA
supplementation in human beings are difficult to interpret because of
the different parameters measured and the variances in dosage,
duration of administration, and subject characteristics (ie, gender,
age, degree of previous termobesity,next term dietary patterns,
activity level).
Supplementation with certain isomers may pose health benefits or risks
to human beings. Before CLA supplementation is recommended for human
beings, controlled research studies using single isomers of CLA need
to be completed to determine its efficacy and safety. |
