Key Takeaways (expand)
- Conjugated linoleic acid, or CLA, is a family of omega-6 fatty acid isomers found mostly in grass-fed meat and dairy products.
- Certain bacteria in the gut can also produce CLA from linoleic and alpha-linolenic acid; however, this conversion can be limited or lost in people with digestive disorders (like celiac disease).
- At least 28 CLA isomers exist, but the most common are cis-9,trans-11 (often just called 9,11) and trans-10,cis12 (often just called 10,12).
- Although technically a trans fat, CLA exerts a number of beneficial health effects for the heart, immune system, gut, and metabolism!
- CLA can interact with the proliferator-activated receptor (PPAR) family—proteins that regulate gene expression by acting as transcription factors.
- By inhibiting PPAR gamma (found in fat cells), CLA is able to increase fat oxidation and reduce fat cell proliferation.
- CLA also increases antioxidant enzyme activity through modulating the expression nuclear factor kappa B (NF-kB).
- Animal studies and in vitro experiments show that CLA may have a protective effect against colorectal cancer, prostate cancer, breast cancer, stomach cancer, and liver cancer, although more research is needed in humans.
- CLA may help improve body composition by reducing appetite, suppressing food intake, inhibiting fat cell production, increasing energy expenditure throughout the body, and stimulating fat breakdown—although these effects seem more pronounced in animal models than in humans.
- The 10,12 CLA isomer may have a more substantial impact on weight loss and fat oxidation than the 9,11 isomer.
- Some evidence suggests CLA could benefit cardiovascular health and reduce the risk of heart attacks, although these effects may be limited to people already at high cardiovascular risk, and/or may be exclusive to the 10,12 isomer.
- CLA (particularly the 9,11 isomer) can improve insulin regulation, though it’s unclear whether supplementation can benefit people with diabetes.
- CLA influences immunity and inflammation by altering cytokine levels and the responses of important inflammatory mediators (like prostaglandin E2).
- Supplementing with CLA has been shown to improve the gut microbiome composition, as well as increase the production of beneficial short-chain fatty acids by gut bacteria!
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Conjugated linoleic acid, or CLA, is a type of omega-6 polyunsaturated fat that’s technically a trans fat (due to the presence of a double bond in the trans configuration). But contrary to what we might expect, it’s widely known as being health-promoting! In fact, CLA behaves so much differently than other trans fats that the FDA exempts it from classification as a trans fat on nutrition labels, and granted it a “Generally Regarded as Safe” designation in 2008!
CLA was first isolated in 1985 by researchers at the University of Wisconsin, who derived it from ground beef extract and identified it as an anti-mutagenic substance. Unlike the trans fats in processed food, which are chemically created from the partial hydrogenation of vegetable oils, CLA is produced as part of the digestive process of ruminant animals (such as cows, sheep, and goats). When these animals consume plant foods, bacteria in their rumens convert linoleic acid (an omega-6 fat) into stearic acid (a saturated fat). Several steps are involved in this process, and one stage involves the production of CLA. Some of this CLA never makes it to the fully saturated stage, and instead becomes incorporated into the animals’ milk and meat (particularly in the non-visible fat distributed along muscle fibers).
CLA exhibits a range of anti-cancer, anti-heart disease, anti-obesity, and anti-diabetes activities, while also serving a beneficial role in immunity and gut health.
The best sources of CLA are meat and dairy products from grass-fed animals—particularly grass-fed beef, grass-fed lamb, butter and cheese from grass-fed dairy, and other full-fat dairy products. Importantly the CLA content of meat and dairy is up to 500% greater when the animals graze on pasture versus eat grain, so while some CLA also exists in grain-fed meat and dairy products, the amount is significantly lower.
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The Biological Roles of CLA
CLA is technically a family of isomers—that is, compounds with the same molecular formula, but with different atom arrangements that result in different biological properties. At least 28 CLA isomers exist, but the most prevalent ones are cis-9,trans-11 (which makes up about 80% of the CLA found in food) and trans-10,cis-12 (which is less abundant, but more efficiently oxidized due to the placement of its double bonds). The majority of existing CLA research has focused on these two isomers.
In humans, the cis-9,trans-11 isomer can induce changes in at least 93 genes, while the trans-10,cis-12 isomer can induce changes in 265 genes. The 9,11 isomer can promote stem cell differentiation, while the 10,12 isomer appears more biologically active when it comes to acting on adipocytes (fat cells), and has also been show to upregulate the LDL receptor in liver cells.
One of CLA’s key features is its ability to interact with the proliferator-activated receptor (PPAR) family—a group of nuclear receptor proteins that regulate gene expression by functioning as transcription factors. CLA can bind to and activate PPAR alpha (which is highly expressed in the liver, kidney, and heart) while inhibiting PPAR gamma (which is found in fat cells, and can moderate triglyceride accumulation and fat cell proliferation). By acting on this system, CLA can affect fat oxidation, inflammation, and glucose metabolism within the body.
CLA also increases antioxidant enzyme activity by modulating the expression of nuclear factor kappa B (NF-kB)—an important transcription factor involved in inflammatory and immune responses. CLA may also increase the activity of certain enzymes involved in fat oxidation, including carnitine palmitoyltransferase-1 (CMPT-1) and acyl-CoA oxidase.
Humans with healthy guts have a (limited!) capacity to obtain CLA from linoleic acid and alpha-linoleic acid, through bioconversion from bacteria in our intestines (particularly Bifidobacteria strains like Bifidobacteria breve). However, studies have shown that people with celiac disease, gut dysbiosis, and other forms of digestive disease lose the ability to produce CLA in any significant amount, so bacterial production isn’t as reliable as dietary intake.
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CLA in Health and Disease
CLA has been studied for its potential role in disease prevention, immunity, and body weight regulation, with findings generally pointing to a beneficial effect—although more so in animal models and in vitro experiments, with human studies being much less consistent (and often in short supply!).
CLA and Cancer
For starters, a variety of studies have explored the relationship between CLA and cancer—not surprisingly, given that its initial discovery pegged it as antimutagenic (meaning it can counteract the effects of things that cause DNA changes). In numerous experiments using both animal models and human cells, CLA has been shown to induce apoptosis (programmed death) of colorectal cancer cells, and some research suggests a protective effect of CLA against breast cancer, prostate cancer, stomach cancer, glioma (brain cancer), and liver cancer. A 2004 study Although a handful of rodent studies found no effect of CLA on cancer, and several even found a tumor-promoting effect of CLA supplementation (particularly in several mouse models of breast cancer), animal research on the whole suggests that CLA is effective as an anti-carcinogen as long as it’s administered early on in cancer development. However, it may be less effective for more advanced tumors.
Scientists are still exploring the mechanisms behind CLA’s anti-cancer effects, but potential routes include the activation of a nuclear receptor protein called peroxisome proliferator-activated receptor gamma (PPARy), an ability to enhance the activity of caspase-3 (a protein that helps regulate programmed cell death) in the colon mucosa, and the inhibition of enzymes involved in tumor invasion. CLA’s ability to alter the metabolism of arachidonic acid (a fat used to produce inflammatory molecules), reduce angiogenesis (the creation of new blood vessels), and exert antioxidant activity could also contribute to a protective effect against cancer.
All that being said, when it comes to research on humans, CLA and cancer studies are in shorter supply—and the ones that do exist have produced inconsistent findings! One trial in women with breast cancer found that CLA supplementation (7.5 g daily for at least 10 days) reduced the expression of a marker of breast cancer proliferation, although there was no effect on other cancer-related proteins. Likewise, a cohort study found a protective association between CLA and breast cancer, and several case-control studies identified a weak cancer-protective effect of CLA (both intake and blood levels) among postmenopausal women. However, additional research in cohorts of French and American women found no association between CLA and breast cancer risk.
It’s possible that the effects of CLA on cancer are nonlinear, with a certain threshold intake required before seeing benefit. This would explain why observational studies of CLA intake often fail to demonstrate a protective effect (since CLA intake among the general public is much lower than the amounts shown to impact cancer), despite clear anti-cancer mechanisms showing up in animal studies and in vitro experiments. Ultimately, more research is needed in humans to understand what groups may benefit most, which types of cancer may be most responsive, and what are intakes are needed to unlock CLA’s potential.
CLA and Obesity
Enormous interest surrounds CLA for its effects on body composition; in fact, CLA is one of the most thoroughly studied weight loss supplements to date! Across a variety of experiments, this fat appears to have a number of anti-obesity effects—including suppressing appetite, reducing food intake, inhibiting adipose fat production, stimulating the breakdown of fat, and increasing energy expenditure throughout the body (including white adipose tissue, muscle, liver tissue, and lean body mass). CLA also shows intriguing potential for simultaneously reducing fat mass while increasing lean body mass.
However, while pre-clinical studies and animal models have often produced promising findings, randomized human trials have been much less consistent. Some of these trials indeed found that CLA from dietary supplements (between 3.4 to 6.8 g daily) was able to reduce body fat mass, abdominal diameter, body weight, and BMI in overweight or obese volunteers—in some cases also increasing lean body mass (AKA muscle mass). One study even found that in conjunction with green tea extract, CLA could help reduce weight gain associated with psychiatric drugs! But, other human trials found no effect on body weight, body composition, or BMI in various populations, ranging from sedentary young women to overweight and obese men. One review of 18 high-quality CLA trials concluded that CLA supplementation (at an average dose of 3.2 g daily) led to only very modest weight loss—about 0.11 lbs. per week, or less than half a pound per month. Another review of longer-term trials (at least six months in duration) concluded that many of the studies had serious flaws in how their methodology was reported, and even then, resulted in weight loss so minor that the clinical relevance was questionable. In all, there have fewer studies showing any significant fat-loss effects of CLA than studies showing no significant effect.
One issue impacting the weight loss results of CLA studies is that different CLA isomers have different effects on body composition. Although most studies include a mixture of CLA isomers, when studied in isolation, the 10,12 isomer has shown a much more pronounced effect on weight loss and oxidation of fat stores (AKA fat burning) than the 9,11 isomer. Some research also shows this isomer promotes the browning of white adipose tissue, contributing to fat mobilization and weight loss. So, CLA isomer type would certainly be expected to impact the results of these studies.
It’s also important to note that humans and research animals have significant differences in the way they biologically respond to CLA—particularly when it comes to weight loss mechanisms. Rodents, in particular, respond more dramatically to PPAR alpha activation (a proposed mechanism for CLA’s weight loss properties) than humans do, which suggests that CLA would have a greater fat-burning effect for these creatures compared to us. So, the promising findings seen in animal studies might not cleanly translate to humans.
Overall, most human trials of CLA supplementation and weight loss have suffered from small sample sizes and relatively short durations, as well as a wide range of different CLA isomer mixtures and dosings. The studies showing benefit have tended to include a continuous dosing strategy (for example, CLA spread out in three smaller daily doses rather than one larger dose each day), as well as a higher proportion of the 10,12 isomer—but even then, the resulting fat loss has generally been minor. Higher-quality human studies with longer durations, differentiation between isomer types, and bigger sample sizes would be helpful for making sense of the conflicting research and determining CLA’s true role in body composition and fat loss!
CLA and Cardiovascular Disease
Limited research suggests that CLA could offer heart-protective benefits. For example, in ApoE knockout mice, CLA supplementation—especially the 10,12 isomer—can prevent atherosclerosis from developing, or even induce its regression after it’s already occurred. Some animal evidence also suggests that CLA can reduce total cholesterol while boosting HDL cholesterol.
Meanwhile, the small amount of human research available on this topic is mixed. In population studies, people with higher tissue levels of CLA appear to have protection against heart attacks and cardiovascular disease in general. However, a controlled trial found that six months of 9,11 CLA supplementation failed to produce any improvements in parameters of atherosclerosis (including blood pressure, C-reactive protein levels, and blood lipids). That being said, the participants in this study were generally healthy and at low cardiovascular risk to begin with, so it’s possible CLA would show a more dramatic effect among people with existing heart disease and/or cardiovascular risk factors. It’s also possible that the 10,12 isomer enacts more heart-protective effects than the 9,11 isomer used in this study. Future research will shed more light on the possibility of CLA playing a heart-protective role in humans!
CLA and Type 2 Diabetes
CLA has also been shown to impact insulin regulation—though the findings here have been both positive and negative. In some animal studies, CLA reduces the pro-inflammatory insulin-resistant state linked to obesity and type 2 diabetes, as well as reduces the size of fat cells. And in humans, higher levels of CLA in adipose tissue (suggesting higher dietary intake) has been associated with a significantly lower risk of diabetes. However, in trials of populations either at high risk of diabetes or who are already diabetic, CLA supplementation failed to produce any improvements in glucose tolerance or insulin sensitivity; in one study of obese women with diabetes, 8 g of CLA daily actually led to fewer improvements than the control (safflower oil)!
Animal studies suggest these inconsistent findings could be due to opposing effects of the 9,11 versus 10,12 isomers on glucose metabolism. Whereas the 9,11 isomer has been shown to increase insulin sensitivity, the 10,12 isomer may actually reduce it, due to causing inflammation within fat cells and preventing the subsequent entry of glucose. More specifically, the 10,12 isomer has been shown to activate the nuclear factor kappaB (NF-kB), in turn inducing an inflammatory molecule called interleukin-6 and ultimately reducing insulin sensitivity. (Intriguingly, this may actually contribute to the weight loss effects of the 10,12 isomer: by hindering the uptake of glucose and fatty acids into fat cells, fat storage is reduced, but at the expense of leaving more glucose to circulate for longer periods of time.) Some studies show that other dietary factors, such as oleic acid, can attenuate this inflammatory effect. So, the whole dietary context is important to take into account!
That being said, human studies haven’t yielded any consistent results when it comes to CLA supplementation and insulin sensitivity or resistance. In one study of 10 sedentary lean men, two participants experienced an increase in insulin sensitivity, six experienced a decrease, and two experienced no significant changes at all in response to 3.2 g of CLA daily. Another small study of overweight, non-diabetic adults yielded similarly mixed findings, with six out of nine participants experiencing a decrease in insulin sensitivity but the remaining three experiencing an increase (in this case, from taking 4 g of CLA daily for 12 weeks). Other studies suggest that at worst, CLA may induce short-term changes in glucose metabolism that return to normal once supplementation is stopped. And, it seems that the insulin desensitizing effects of CLA are mostly apparent when carbohydrates are simultaneously consumed, with the effects being negligible under other circumstances. It’s also likely that factors like age and genetics (including individual variation in the PPAR system) contribute to how CLA supplementation impacts insulin sensitivity.
So, while mechanisms do exist by which CLA (particularly the 10,12 isomer) could have a harmful effect on glucose metabolism, human research hasn’t shown this to be a huge area concern. More studies are needed to understand any potential risks here!
CLA and Immunity
Additional benefits of CLA involve its effects on the immune system. Studies show that CLA can alter immune responses by reducing an important inflammatory mediator called prostaglandin E2, decreasing tissue levels of arachidonic acid (a fat used for the synthesis of inflammatory molecules), and reducing the negative effects of endotoxin (a harmful component of certain bacteria cell membranes) during infection.
In a study of healthy adults, CLA supplementation (a total of 3 g daily for 12 weeks) was able to increase blood levels of IgA (an antibody that plays an immune role in mucous membranes) and IgM (the first antibody that the body makes during an immune response), while lowering levels of IgE (an antibody that mediates allergic reactions). Here, CLA also lowered levels of two pro-inflammatory cytokines (TNF-alpha and IL-1beta) while increasing an anti-inflammatory cytokine called IL-10. These findings point to a beneficial effect of CLA on immunity, but more research is needed in humans to confirm it.
CLA and Gut Health
Lastly, CLA is emerging as a potential aid in gut health. Animal studies have shown that supplementation with the 10,12 isomer of CLA can alter the composition of the gut microbiota (including enriching levels of Butyrivibrio, Roseburia, and Lactobacillus species), as well as increase the production of beneficial short-chain fatty acids (particularly butyrate). There’s even some evidence that CLA can modify the gut microbiota in ways associated with weight loss and improved insulin sensitivity, providing another mechanism by which CLA could benefit weight loss (and possibly counteracting any pro-diabetic effect).
CLA and Asthma
CLA could benefit patients with asthma. A 2010 clinical trial found that among overweight mild asthmatics, supplementation with 4.5 g of CLA daily for 12 weeks led to significant improvements in airway hyper-responsiveness, relative to the placebo group. Mechanistic studies have demonstrated that CLA exerts anti-inflammatory effects in bronchial epithelial cells by inhibiting proinflammatory cytokines, chemokines, and ICAM-1 expression, as well as by reducing eicosanoid precursors.
CLA and Inflammatory Bowel Disease
A number of studies have shown that CLA can benefit inflammatory bowel diseases, including Crohn’s disease.
A small 2012 trial found that among people with mild to moderately active Crohn’s disease, 12 weeks of CLA supplementation (6 g daily) led to lower production of pro-inflammatory cytokines, in turn reducing disease activity and improving patients’ quality of life.
Animal models of Crohn’s disease suggest these anti-inflammatory effects could be due, at least in part, to modulating the gut microbiota, with downstream effects on the nuclear receptor PPAR-gamma.
CLA and Rheumatoid Arthritis
Some evidence suggests CLA could benefit rheumatoid arthritis. A 2014 double-blind controlled trial found that CLA, especially when combined with vitamin E, was able to lower markers of inflammation in rheumatoid arthritis patients. And, a small 2016 randomized controlled trial showed that among patients with active rheumatoid arthritis, supplementation with 2 g of CLA daily (in addition to standard treatment) had a positive effect on bone markers, compared to standard treatment alone. Specifically, the CLA led to improved activity of telopeptides C, osteocalcin, and IGF-1! Rodent models of rheumatoid arthritis have also shown a powerful effect of CLA on disease symptoms, including significantly reducing arthritic scores, delaying the onset of arthritis, and reducing markers of inflammation.
The THREE Best Probiotics
Bacillus/Spore-based
Best for a general probiotic, if you were recently on antibiotics, or for digestion issues (especially abdominal pain, bloating, flatulence, diarrhea, and gas after meals).
Lactobacillus & Bifidobacterium
Best for if you don’t eat fermented foods, if you were recently on antibiotics, or if you have issues with constipation or gas.
Saccharomyces boulardii
Best for if you have Candida issues, were recently on antibiotics, or have diarrhea.
Health Effects of CLA Deficiency
Because CLA isn’t an essential fat, there aren’t any true deficiency diseases associated with low intake. However, dietary estimates show that the average adult only consumes between one third and one half the amount of CLA shown in produce benefits in studies (such as cancer reduction); in the US, average daily consumption is 151 mg for women and 212 mg for men. It’s possible that low intake can impair a person’s fat burning capacity.
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How Much CLA Do We Need?
There’s no recommended intake guidelines for dietary CLA. However, consuming CLA in the range of 3.2 to 6.4 g daily is likely to produce the clinical benefits seen in studies. So far, intakes higher than this haven’t been shown to produce any additional health effects!
It’s also worth noting that the CLA sold as supplements isn’t derived from foods, but rather, is made through the chemical alteration of linoleic acid in vegetable oils—leading to different proportions of isoforms than those naturally occurring in meat and dairy. Not surprisingly, research on CLA supplements generally show them to be less beneficial than CLA obtained from foods, and some studies even suggest adverse effects from supplementation (such as higher C-reactive protein, a bloodborne marker of inflammation). And, CLA in only one isoform may be particularly unhelpful, because the different isoforms appear to work synergistically to provide benefits.
While CLA supplements are unlikely to cause serious side effects, some people report nausea, upset stomach, fatigue, and diarrhea, especially when taken in high doses.
Nutrient Daily Values
Nutrition requirements and recommended nutrient intake for infants, children, adolescents, adults, mature adults, and pregnant and lactating individuals.
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Good Food Sources of CLA
The following foods are good sources of CLA, containing at least 0.07 grams per serving.
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