Ian Goddard <[email hidden]> wrote in message
news:<[email hidden]>...
Quoted message said:I've been impressed with the many potential health benefits of conjugated linoleic acid (CLA):
sciencenews.orgbob9.aspOpen ↗
However, last night I ran into the following studies that raise concerns for me. These studies
found that the active CLA isomer increased several major pro-aging markers in obese humans.
Specifically, CLA increased C-reactive protein, lipid peroxidation, and insulin resistance. The
latter marker being quite unexpected given animal research (and one human study cited at the
bottom of this post) suggesting improved insulin sensitivity. What's up with that?
I'm not sure how to interpret this data, but given that each of the cited pro-aging markers that
CLA increased are exactly what life-extenders should wish to decease, I'm posting this data to
encourage productive feedback and discussion.
Hi Ian, I stopped taking it a couple of years ago based pretty much on the same concerns. Here is
what I have saved on it. My info duplicates and supports yours. If I were a fat diabetic I might
reconsider. The references to Tom in my records are from the old LEF forum and refer to Paul. The
reason I reinvestigated it and stopped is that he had stopped. This is what I have on it. Thomas
DEF: CLA: Found in red meat. Anti cancer, good for blood sugar. Prevents muscle wasting.
Antioxidant. I have been watching this for a year or two. This paper is definitive for me, unless
some really great studies come along. Diabetes Care 2002 Sep;25(9):1516-21 Treatment with dietary
trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with
the metabolic syndrome. Riserus U, Arner P, Brismar K, Vessby B. Department of Public Health and
Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden. [email hidden]
OBJECTIVE: Conjugated linoleic acid (CLA) is a group of dietary fatty acids with antiobesity and
antidiabetic effects in some animals. The trans10cis12 (t10c12) CLA isomer seems to cause these
effects, including improved insulin sensitivity. Whether such isomer-specific effects occur in
humans is unknown. The aim of this study was to investigate whether t10c12 CLA or a commercial CLA
mixture could improve insulin sensitivity, lipid metabolism, or body composition in obese men with
signs of the metabolic syndrome. RESEARCH DESIGN AND METHODS: In a randomized, double-blind
controlled trial, abdominally obese men (n = 60) were treated with 3.4 g/day CLA (isomer mixture),
purified t10c12 CLA, or placebo. Euglycemic-hyperinsulinemic clamp, serum hormones, lipids, and
anthropometry were assessed before and after 12 weeks of treatment. RESULTS: Baseline metabolic
status was similar between groups. Unexpectedly, t10c12 CLA increased insulin resistance (19%; P <
0.01) and glycemia (4%; P < 0.001) and reduced HDL cholesterol (-4%; P < .01) compared with
placebo, whereas body fat, sagittal abdominal diameter, and weight decreased versus baseline, but
the difference was not significantly different from placebo. The CLA mixture did not change glucose
metabolism, body composition, or weight compared with placebo but lowered HDL cholesterol (-2%; P <
0.05). CONCLUSIONS: These results reveal important isomer-specific metabolic actions of CLA in
abdominally obese humans. A CLA-induced insulin resistance has previously been described only in
lipodystrophic mice. Considering the use of CLA-supplements among obese individuals, it is
important to clarify the clinical consequences of these results, but they also provide
physiological insights into the role of specific dietary fatty acids as modulators of insulin
resistance in humans. PMID: 12196420
The Good transFat Will one family of animal fats become a medicine? 2001 Over the past 4
years, a new and surprising dietary supplement has been edging its way onto the shelves of
health-food stores. Known as CLA, it's a mixture of trans fats, compounds usually associated
with raising the concentration of cholesterol in people's blood. The acronym, for conjugated
linoleic acid, signifies that the fats in CLA are unusual forms of the essential nutrient
linoleic acid. The first potential health effect of CLA emerged 17 years ago, when Michael
W. Pariza of the University of Wisconsin-Madison announced that he had isolated an
unidentified agent in hamburger that reduced the incidence of cancer in mice (SN:
12/22&29/84, p. 390). Four years later, his team unmasked the mystery agent: one chemical
form, or isomer, of linoleic acid. But nobody's laughing about it now. Several hundred
published studies of CLA's effects in animals and a few preliminary experiments with people
have since suggested an array of health benefits from the unusual trans fats. Linoleic acid
is a kinked molecule built around a chain of 18 carbon atoms. Most of the links coupling
each carbon to its neighbors are known as single bonds. Two of the links in the chain are
the more rigid double bonds. Various chemical reactions can induce one of the double bonds
to shift so that it is separated from the other by only one single bond. The molecule that
results is called a conjugated fatty acid. Of the different CLA isomers that can form, just
two have been linked to health effects. One's called cis-9, trans-11 (c9-t11), and the
other, trans-10, cis-12 (t10-c12). Isolating each of these isomers is difficult and
expensive. Most tests therefore use a mixture of the two that's commercially produced from a
vegetable oil. Experiments in animals have revealed the mystery cancer fighter that Pariza
discovered in hamburger 17 years ago to be c9-t11. It continues to be the most frequently
studied of CLA's isomers. Potential health value His team gave 3-grams of off-the-shelf CLA
supplements daily to half of the 80 clinically obese men and women enrolled in a
weight-reduction trial. The remaining volunteers received identical capsules filled with
sunflower oil. Animal studies had shown that only the t10-c12 alters fat accumulation, but
to keep costs down the researchers used a 50:50 supplement of it and the C9-t11. Both
dieting groups also received advice on cutting calories and upping their exercise. By the
end of 6 months, all the participants had lost weight--on average about 5 pounds each.
However, one-third of those taking the CLA, but only one-sixth of the others, increased
muscle mass. CLA caused the dieter's bodies to partition more of the energy from food into
lean tissue, not fat, says Pariza. Ola Gudmundsen of Scandinavian Clinical Research AS in
Kjeller, Norway, and his colleagues reported similar data on 60 overweight or obese
volunteers in a 3-month dieting trial. Groups of 12 men and women, 40 to 50 years old,
received daily capsules containing either 9 g of olive oil or a dose of 1.7 to 6.8 g of CLA.
As in Pariza's trial, the CLA supplement was roughly a 50:50 mix of the c9-t11 and t10-c12
isomers. Even in this short trial, people getting 3.4 g or more of CLA per day ended up
weighing 2 to 3 pounds less than the others, Gudmundsen says. Dieters reaped no extra
benefits from downing more than 3.4 g of CLA per day, his team reports in the December 2000
Journal of Nutrition. The group receiving the highest dose of CLA did, however, develop
slightly more lean tissue than the other groups did. Diabetes and large doses Larger doses
of the 50:50 CLA formulation hold out tantalizing prospects for helping people with type II
diabetes, according to another trial reported at the ACS meeting. Martha Belury of Northwest
Hospital in Seattle and her colleagues at Purdue University in West Lafayette, Ind., tested
nine people who have this adult-onset form of diabetes. The researchers gave them daily
capsules containing either 6 g of safflower oil or CLA daily for 8 weeks. Fasting blood
sugar, or glucose, was moderately improved in people getting the CLA supplements but not in
those getting the safflower oil. Similarly, only the CLA group experienced a significant
lowering in blood concentration of triglycerides,. "We also saw this beneficial triglyceride
lowering" in a study with diabetic rats, Belury notes. "Most exciting and definitely the
most significant, statistically," she says, was the finding that people taking the CLA
supplement had lower blood concentrations of the hormone leptin compared with the volunteers
taking safflower oil. Other researchers have associated elevations in blood leptin
concentrations with obesity. To Belury, her provocative leptin data "suggest CLA may act on
type II diabetes via some mechanism affecting [body-]fat accumulation." Why did Belury
consider studying CLA's effects on diabetes? Her team's molecular studies several years ago
showed that CLA shares properties with some drugs. "We think CLA binds to a [cellular]
receptor that is similar to one that some antidiabetes drugs target," Belury explains.
Wondering whether the nutritional supplement would act similarly to these drugs, she and her
colleagues administered the fat supplements to rats predisposed to developing diabetes. To
her surprise, Belury notes, "CLA actually delayed the onset of diabetes." Slowing plaque
buildup In studies with rabbits, he had been looking for agents that don't just slow a
potentially deadly buildup of plaque along artery walls but actually make these fatty
deposits regress. With other chemical agents, he says, "if you find something that gives you
a few percent regression, you do handsprings. In our studies with [a 50:50 formulation of]
CLA, we saw a 30 percent reduction [in existing plaque]--which is nothing less than
phenomenal." Figuring that such a result was too good to be true, Kritchevsky repeated the
experiments. Again, he fed the rabbits plaque-forming diets for 3 months. He then killed
one-third of the animals to measure their plaque buildup. Over the next 3 months, the
surviving animals ate either a normal diet or one containing from 0.1 to 1 percent CLA, by
weight of food. When compared with the unsupplemented animals, rabbits getting the 0.1
percent-CLA diets had a little less plaque. However, those getting chow that was 1 percent
CLA had 30 percent less plaque, he reported in an April 2000 supplement of the Journal of
The American College of Nutrition. A feed supplement A little more than a decade ago, while
looking for a low-cost feed supplement, animal scientist Mark E. Cook and his colleagues at
the University of Wisconsin-Madison stumbled onto CLA's immune-enhancing attributes.
. When a vaccine stimulates the animals' immune system, it triggers an inflammatory action, which
produces proteins that induce muscle wasting. Some of these same cytokines, such as tumor necrosis
factor, cause wasting in cancer patients. "We were hoping to find something to cut the
inflammatory reaction that led to wasting," Cook says. Since compounds fashioned from linoleic
acid participate in the chain of signals that induce wasting, he wondered whether CLA--as altered
linoleic acids--might somehow mute the vaccine's inflammatory effect. So, he fed animals either a
normal diet or one supplemented with the
50:50 CLA mix and then injected each with an immunity stimulant. "It worked," Cook crows. "CLA
totally blocked the [temporary] wasting" in rats, mice, chicks, and pigs, without reducing their
ability to fight disease. While that looked like a possible boon to meat producers, the earlier
findings had prompted Cook to worry whether people taking CLA supplements might compromise their
immunity. So, he encouraged his colleagues to probe how the mixture of trans fats perturbs an
animal's immune system. In a series of patent applications, his team reports that CLA
dramatically increases several families of infection-fighting white blood cells, including a type
known as natural killer cells. When the body isn't under assault, however, CLA appears to dampen
down the natural background level of immune stimulation. Such a dampening, Cook notes, is usually
a good thing. Most recently, Cook's team has shown that CLA appears to derail allergic reactions
by selectively dampening--as several drugs do--the activity of cyclooxygenase-2 (COX-2), an
enzyme that triggers many types of inflammation. Indeed, Cook told Science News, "we're quite
excited and have just patented CLA as a COX-2 inhibitor." Animal studies Data from animal studies
have consistently shown CLA's anticancer promise. For example, Clement Ip of the Roswell Park
Cancer Institute in Buffalo, N.Y., recently showed that butter enriched in c9-t11 cut the risk of
mammary cancer in rats that ate it (SN: 12/11/99, p. 375). Researchers don't know whether CLA
isomers other than c9-t11 have anticancer effects. Right now, Ip says, "we have almost no
[animal] data on the t10-c12, in terms of cancer protection." Is it now time to begin studies to
see if CLA supplements can prevent cancer in people? "Not quite," Ip says emphatically.
References: Belury, M.A., A. Mahon, and L. Shi. Role of conjugated linoleic acid
(CLA) in the management of type 2 diabetes: Evidence from Zucker diabetic (fa/fa) rats and human
subjects (Abstract AGFD 26). American Chemical Society 220th National Meeting. August 20-24.
Washington,
D.C.Blankson, H. . . .and O. Gudmundsen. 2000. Conjugated linoleic acid reduces body fat mass in
overweight and obese humans. Journal of Nutrition 130(December):2943. Blankson, H. . . .and O.
Gudmundsen. 2000. Effects of conjugated linoleic acid (CLA) on body fat mass in overweight or
obese human volunteers: A double-blind, randomized placebo controlled study(Abstract AGFD 23).
American Chemical Society 220th National Meeting. August 20-24. Washington, D.C. Cook, M.E., et
al. 2000. Regulation of inducible prostranoids and leukotrienes by conjugated linoleic acid
(CLA) (Abstract AGFD 10). American Chemical Society 220th National Meeting. August 20-24.
Washington, D.C. Hurst, W.J., et al. In press. Determination of conjugated linoleic acid (CLA)
concentrations in milk chocolate. Journal of Agricultural and Food Chemistry. Kritchevsky, D.
2000. Influence of conjugated linoleic acid (CLA) on experimental atherosclerosis (Abstract AGFD
14). American Chemical Society 220th National Meeting. August 20-24. Washington, D.C.
Kritchevsky, D., et al. 2000. Influence of conjugated linoleic acid
(CLA) on establishment and progression of atherosclerosis in rabbits. Journal of the American
College of Nutrition 19(April):472S. Pariza, M.W. 2000. Conjugated linoleic acid: The paradox
of multifunctionality (Abstract AGFD 9). American Chemical Society 220th National Meeting.
August 20-24. Washington, D.C. Park, Y. . . .and M.W. Pariza. 1999. Evidence that the
trans-10, cis-12 isomer of conjugated linoleic acid induces body composition changes in mice.
Lipids 34(March):235. Further Readings: Bee, G. 2000. Dietary conjugated linoleic acid
consumption during pregnancy and lactation influences growth and tissue composition in weaned
pigs. Journal of Nutrition 130:2981. ______. 2000. Dietary conjugated linoleic acids alter
adipose tissue and milk lipids of pregnant and lactating sows. Journal of Nutrition
130:2292.
Tom, What do you think about his study on CLA...Isn't TNFa bad as well as increased insulin
resistance? And the hepatomegaly is worrisome as well. I am reading too much here? Thanks!
Diabetes, September 2000 Volume 49, Number 9 Conjugated Linoleic Acid Supplementation Reduces
Adipose Tissue by Apoptosis and Develops Lipodystrophy in Mice Nobuyo Tsuboyama-Kasaoka, Mayumi
Takahashi, Kentaro Tanemura, Hyoun-Ju Kim, Tsuyoshi Tange Hitoshi Okuyama, Masaaki Kasai, Shinji
Ikemoto, Osamu Ezaki
Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic
acid found in beef and dairy products. CLA has been reported to reduce body fat. To examine the
mechanism(s) of CLA reduction of fat mass, female C57BL/6J mice were fed standard semipurified diets
(10% fat of total energy) with or without CLA (1% wt/wt). Terminal deoxynucleotidyl
transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and DNA fragmentation analysis revealed
that fat-mass decrease by CLA was mainly due to apoptosis.
[ Apoptosis (programmed cell death) of fat cells is beneficial, since one major problem with obesity
is that once fat cells accumulate it is hard to reduce their number. Dieting generally only reduces
the size of each making the regaining of weight very easy indeed. -- Tom ]
Tumor necrosis factor (TNF)- and uncoupling protein (UCP)-2 mRNA levels increased 12- and 6-fold,
respectively, in isolated adipocytes from CLA-fed mice compared with control mice. Because it is
known that TNF- induces apoptosis of adipocytes and upregulates UCP2 mRNA, a marked increase of TNF-
mRNA with an increase of UCP2 in adipocytes caused CLA-induced apoptosis. However, with a decrease
of fat mass, CLA supplementation resulted in a state resembling lipoatrophic diabetes: ablation of
brown adipose tissue, a marked reduction of white adipose tissue, marked hepatomegaly, and marked
insulin resistance. CLA supplementation decreased blood leptin levels, but continuous leptin
infusion reversed hyperinsulinemia, indicating that leptin depletion contributes to the development
of insulin resistance. These results demonstrate that intake of CLA reduces adipose tissue by
apoptosis and results in lipodystrophy, but hyperinsulinemia by CLA can be normalized by leptin
administration. Diabetes 49:1534–1542, 2000
[ Thanks for this abstract. It strongly suggests that while CLA may be important for weight
reduction and fighting cancer, but should not be used by healthy thin people. I will be seriously
checking this out, with a view to ceasing my current intake of CLA. -- Tom ] Biochem Biophys Res
Commun 1998 Mar 27;244(3):678-82 Erratum in: Biochem Biophys Res Commun 1998 Jun 29;247(3):911
Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the Zucker diabetic fatty
fa/fa rat. Houseknecht KL, Vanden Heuvel JP, Moya-Camarena SY, Portocarrero CP, Peck LW, Nickel KP,
Belury MA. Department of Animal Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Conjugated linoleic acid (CLA) is a naturally occurring fatty acid which has anti-carcinogenic and
anti-atherogenic properties. CLA activates PPAR alpha in liver, and shares functional similarities
to ligands of PPAR gamma, the thiazolidinediones, which are potent insulin sensitizers. We provide
the first evidence that CLA is able to normalize impaired glucose tolerance and improve
hyperinsulinemia in the pre-diabetic ZDF rat. Additionally, dietary CLA increased steady state
levels of aP2 mRNA in adipose tissue of fatty ZDF rats compared to controls, consistent with
activation of PPAR gamma. The insulin sensitizing effects of CLA are due, at least in part, to
activation of PPAR gamma since increasing levels of CLA induced a dose-dependent transactivation of
PPAR gamma in CV-1 cells cotransfected with PPAR gamma and PPRE X 3-luciferase reporter construct.
CLA effects on glucose tolerance and glucose homeostasis indicate that dietary CLA may prove to be
an important therapy for the prevention and treatment of NIDDM. PMID: 9535724 Int J Obes Relat Metab
Disord 2001 Aug;25(8):1129-35 Conjugated linoleic acid (CLA) reduced abdominal adipose tissue in
obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial. Riserus
U, Berglund L, Vessby B. Clinical Nutrition Research Unit, Department of Public Health and Caring
Sciences/Geriatrics, Faculty of Medicine, Uppsala University, Uppsala, Sweden.
[email hidden] BACKGROUND: Abdominal obesity is strongly related to metabolic
disorders. Recent research suggests that dietary conjugated linoleic acid (CLA) reduces body fat and
may improve metabolic variables in animals. The metabolic effects of CLA in abdominally obese humans
have not yet been tested. OBJECTIVE: To investigate the short-term effect of CLA on abdominal fat
and cardiovascular risk factors in middle-aged men with metabolic disorders. METHODS: Twenty-five
abdominally obese men (waist-to-hip ratio (WHR), 1.05+/-0.05; body mass index (BMI), 32+/-2.7
kg/m(2) (mean+/-s.d.)) who were between 39 and 64-y-old participated in a double-blind randomised
controlled trial for 4 weeks. Fourteen men received 4.2 g CLA/day and 10 men received a placebo. The
main endpoints were differences between the two groups in sagittal abdominal diameter (SAD), serum
cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, free fatty acids,
glucose and insulin. RESULTS: At baseline, there were no significant differences between groups in
anthropometric or metabolic variables. After 4 weeks there was a significant decrease in SAD (cm) in
the CLA group compared to placebo (P=0.04, 95% CI; -1.12, -0.02). Other measurements of
anthropometry or metabolism showed no significant differences between the groups. CONCLUSIONS: These
results indicate that CLA supplementation for 4 weeks in obese men with the metabolic syndrome may
decrease abdominal fat, without concomitant effects on overall obesity or other cardiovascular risk
factors. Because of the limited sample size, the effects of CLA in abdominal obesity need to be
further investigated in larger trials with longer duration. Publication Types: Clinical Trial
Randomized Controlled Trial PMID: 11477497
See lef.orgapril00 cover.htmlOpen ↗
forum.lef.orgreadTopic.cgiOpen ↗
lef.orgoct2001 report coq10 01.htmlOpen ↗ for the LEF discussion. It comes in
three parts.
$Taking 700mg in 2000 in 2000 LE is recommending 3000 mg Stoped taking in Mar. 2001 $To Take?
