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.
Though manufacturers of CLA can’t legally make health claims for their products, they often point to recent scientific articles–which they occasionally post next to their products–indicating a growing list of possible health benefits from CLA. These include fighting cancer, enhancing immunity, and ridding the body of fatty, artery-clogging plaque.
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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.
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Pariza and other researchers soon found that dairy products also contain a mixture of isomers that they began calling CLA. Some concentrations of CLA in dairy products were similar to those in ground beef. Indeed, Pariza’s research temporarily became the butt of more than a few jokes when it identified the richest dairy source of CLA as none other than Cheez Whiz (r) (SN: 2/11/89, p. 87).
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.
David Kritchevsky of the Wistar Institute in Philadelphia sees more than a little irony here. In recent years, animal fats have been scorned as promoters of chronic disease. The possibility that the trans fats in CLA offer health benefits and are naturally “only found in animal fat is proof God has a sense of humor,” he says.
A kinked molecule
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. There are several dozen of these CLA isomers that differ in the placement of the double bonds and the kinks in the chain. Their names indicate where the double bonds lie along the molecule and whether there’s a kink at that spot (a cis double bond) or no kink (a trans double bond).
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
While there haven’t yet been trials of CLA’s cancer-fighting potential in people, scientists have begun human trials to investigate the fats’ potential value in other health applications. For instance, at an American Chemical Society (ACS) meeting last fall in Washington, D.C., Pariza presented encouraging, albeit preliminary, findings from a study aimed at helping people battle the bulge.
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.
“Every fat cell in the body wants to get big,” he explains. “What the t10-c12 CLA does is force that fat cell to stay little by affecting a number of the enzymes that are ordinarily responsible for filling it with lipids.”
So, while this isomer doesn’t seem to help dieters shed fat, he speculates that it could help prevent their regaining fat lost by dieting or exercise.
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.
As in the other human trials reported at the meeting, neither the volunteers nor the researchers knew who got CLA until the study ended. “But when we broke the code [identifying the CLA group],” Belury recalls, “our data screamed at us.”
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, which are groups of fats known to increase the risk of heart disease. “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.”
Observes Belury, “Most diabetes drugs today are so potent that they literally have toxic side effects.” If CLA offers pharmaceutical benefits without the toxicity, she argues, it may provide some individuals with an alternative to these drugs–or at least a way to ratchet down their drug doses.
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
Some other potential benefits of CLA have turned up in animal experiments. Kritchevsky, for example, recently reported evidence of CLA targeting atherosclerotic plaque.
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.
“In animal experiments, nobody has ever reported anything like this,” emphasizes Kritchevsky. “This stuff is just amazing.”
In this application, Kritchevsky doesn’t know which isomer is active.
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.
Poultry producers typically vaccinate young chickens to ward off epidemics. However, “you lose about a day’s growth every time you vaccinate a chicken,” notes Cook. Worldwide, he estimates, this seemingly small extension in the time it takes to get chickens to market “probably costs growers $1 billion a year.”
Although they didn’t know how to avoid it, Cook and others knew what causes the growth halt in the chickens. 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.
Findings in several other animal studies, soon to be published, indicate that CLA supplements may control allergies. In one experiment, Cook’s group sensitized guinea pigs to allergens to serve as models of allergic asthma. When the researchers exposed the animals’ airways to the allergens, dramatically less airway constriction occurred if the animals had been fed CLA.
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.”
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.
Human cancer trials of CLA will be difficult, he explains, because researchers don’t know how to measure the isomers’ immediate effects. Because malignancies typically take decades to develop, tracking cancer incidence in people taking a nutritional supplement is impractical.
Instead, most human trials monitor the relatively rapid development of precancerous biomarkers, such as elevated concentrations of enzymes, cell changes, or activation of certain genes. Right now, Ip points out, “we don’t have good information on what biomarkers will respond to CLA in humans, so we wouldn’t know what to look for.”
He also points out that the animal work hasn’t indicated what types of human cancers might be most responsive.
Boosting natural concentrations
At doses achievable in an ordinary diet, CLA doesn’t appear to have the power to bring about any of the reported health benefits. Several research teams have undertaken major programs to boost natural concentrations of c9-t11 in meat and dairy products. But even enriched foods may not contain enough CLA to offer a potent barrier to disease.
Hence, the rush by many supplement makers to market megadose formulations. Capsules now on sale contain about 1 g of CLA. However, most researchers argue that while these pricey supplements probably aren’t harmful, they may not deliver desired benefits.
Not only have few trials confirmed that CLA works in people as it does in animals, but currently marketed CLA recipes may not be appropriate to deliver the hoped-for benefits. At present, manufacturers base their recipes mostly on what’s least expensive to make.
Manufacturers typically synthesize CLA from linoleic acid, or from oleic acid, the principal fat in olive oil, notes Gerald P. McNeill, technical director for Loders Croklaan North America in Channahon, Ill. Its Dutch parent company is a leading producer of CLA.
In the early days, manufacturers relied on toxic solvents and aggressive catalysts to affordably produce CLA, McNeill explains. However, the processes were so harsh that they typically yielded “about 25 different [CLA] isomers in significant quantities,” he notes.
“We changed to a gentler methodology,” he told Science News. With it, his company has been able to make 95 percent of its CLA as a roughly equal mix of c9-t11 and t10-c12.
In theory, he says, it’s possible to separate the two isomers. “We’ve even done it on a pilot scale,” he acknowledges. “But it cost us a wagon-load of money.” As in any separation process, the expense of the first couple kilograms was more than that of an equal weight of platinum.
If a demand for pure isomers develops, McNeill says, it might be possible to bring costs down. For now, even researchers usually just settle for the best that they can afford: a 50:50 mix.
However, getting even a 50:50 mix of the two target isomers can depend on the manufacturer, which isn’t always noted on the label. Pariza points out that he conducts studies using CLA only from Loders Croklaan and Natural Inc. of Sandvika, Norway. These two manufacturers routinely submit their products to his tests to ensure they’re a 50:50 mix of c9-t11 and t10-c12 isomers.
Several years ago, similar tests on CLA by Peter Yurawecz of the Food and Drug Administration in Washington, D.C., showed some off-the-shelf health-store products wanting. He sampled 15 bottles.
“One was a bogus product” containing no CLA, he says. Several others contained about 90 percent CLA in the intended 50:50 mix. However, he says, a lot of the remaining products showed different proportions and included isomers “with various cis-trans configurations.”
Warns Pariza , “Buyer beware” remains a prudent policy.