For Patients & Caregivers
How It Works
Although Conjugated Linoleic Acid (CLA) is marketed as a supplement for weight loss and to lower cholesterol levels, human studies on potential benefits are limited and mixed.
CLA is commonly found in dairy products and beef, and is made by microbes that live within the gut of certain animals. It is also found throughout the body. CLA is often marketed as a supplement for weight loss.
Animal studies suggest CLA supplementation may improve insulin sensitivity and blood lipid profiles, decrease body fat, and reduce risks for cancer and cardiovascular disease. However, many of these effects have not been replicated in humans, or studies show mixed results. In addition, there is also a concern for potential increase risk of cardiovascular disease with high CLA intake. Therefore more well-designed studies are needed to determine under what conditions CLA supplementation demonstrates safety and any benefits.
- To prevent and treat cancer Although animal studies suggest CLA has antioxidant properties and may reduce cancer risk, studies in humans are limited and mixed. Therefore, clinical trials to confirm safety and effectiveness are needed.
- To treat high cholesterol Although a few studies suggest CLA may reduce a type of fat in the blood called triacylglycerols, it was shown to increase total cholesterol and may also reduce HDL, or good cholesterol levels.
- To promote healthy weight CLA may improve body fat mass in some people, but results are mixed, and CLA may actually be harmful in some populations. For example, in obese men with metabolic syndrome or at high risk for heart disease, CLA supplementation decreased insulin sensitivity or caused insulin resistance. In addition, it does not appear to enhance the benefits of exercise.
Do Not Take If
- Gastrointestinal symptoms
- Migraine visual disturbance: In an older adult man without prior migraine history, and related to several separate instances of taking a CLA supplement.
- Sudden, intense headache: In a 50-year-old black woman after starting an herbal weight loss supplement containing CLA, green tea, and L-carnitine.
For Healthcare Professionals
Conjugated Linoleic Acid (CLA) is a naturally occurring fatty acid found in the milk and meat of ruminant animals (22). CLA supplements have been marketed for weight control and to lower high cholesterol. Other purported uses include cancer prevention. CLA has different isomers that appear to have distinct characteristics, with anticarcinogenic effects more likely attributable to cis-9,trans-11 and antiobesity effects attributable to the trans-10,cis-12 (23) isomer.
In humans, studies on potential benefits are mixed. Preliminary data suggest CLA supplementation may improve some markers related to bone health in patients with rheumatoid arthritis (47). Other small studies suggest some benefit in COPD (48) (49), as an adjunct to usual care in mild asthmatics (21), or antithrombotic or antiatherosclerotic effects in overweight adults (24). However, cis-9,trans-11 CLA supplementation decreased insulin sensitivity in obese men at high risk for cardiovascular disease (25), and short-term high-CLA intake did not affect blood pressure regulation in healthy volunteers (27). Another study also suggests no effects on antioxidant metabolism in overweight/obese individuals (26), and meta-analyses indicate proinflammatory effects (50) (51). And although data suggest CLA can lower triacylglycerol levels (22) (35), other studies indicate it can increase the total-to-HDL cholesterol ratio and lower HDL levels (58).
Preliminary studies on CLA-induced changes in body composition and weight reduction are also mixed, with some yielding positive results (28) (29) (30) while others do not show benefits (31) (32) (46). Although meta-analyses suggest effects on serum leptin levels in certain subgroups (52) (53), it did not affect fasting blood glucose or waist circumference in healthy adults (54). CLA also did not impact aerobic capacity (33), aerobically-induced neuromuscular fatigue (34), or exercise performance (35).
Animal studies suggest that CLA may play a role in reducing tumor proliferation in certain cancer cell lines (2) (3) (4). In models of colorectal cancer, CLA reduced inflammation and decreased disease activity (36) (37). Preliminary human studies suggest anticancer effects with CLA in colorectal (38) and breast (39) cancers, but a meta-analysis found no association between CLA intake and reduced breast cancer risk (55). More studies in the context of clinical trials are needed.
Mechanism of Action
Of several possible CLA isomers, cis-9,trans-11 and trans-10,cis-12 are the main isomers found in meat and dairy products, as well as commercial supplements. They appear to have distinct characteristics, with anticarcinogenic effects more likely attributable to cis-9,trans-11 and antiobesity effects attributable to trans-10,cis-12 (23).
CLA reduced prostaglandin synthesis, especially PGE2 (12) (13), and decreased stearoyl-CoA desaturase activity (14). The trans-10,cis-12 isomer decreased serum HDL cholesterol levels (9), inhibited stearoyl-CoA desaturase activity (12), and decreased insulin-like growth factor-II secretion at both transcriptional and post-transcriptional levels (18).
Laboratory and animal studies suggest that CLA has both anti- and pro-oxidant effects (40) (41). CLA may reduce abdominal adiposity through increased energy expenditure, while myocardial oxidative stress may occur through changes in transmembrane potential or the antioxidant defense system (40).
In humans, CLA appeared to have a synergistic effect with a mixture of oleic and erucic acids in reducing neuroinflammation and enhancing peroxisomal beta-oxidation (42). In human skeletal muscle, CLA enhanced the rate of glycogen resynthesis after exercise (43).
It is thought that replacing other polyunsaturated fatty acids (PUFAs) with CLA may reduce oxidative stress and modulate intracellular signaling (11). These effects may inhibit carcinogenesis and affect cellular responses to tumor necrosis factor-alpha (TNF-alpha) (15). In vitro, CLA inhibited MCF-7 breast cancer cell proliferation, but the mechanisms by which this occurred for both isomers (trans-10,cis-12 and cis-9,trans-11) differed and require future elucidation (3). The cis-9,trans-11 isomer induced tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 mRNA in SGC-7901 human gastric carcinoma cells, which may play a role in inhibiting the tumor metastasis cascade (2). This inhibition may come from blocking the cell cycle with reduced expressions of cyclin A, B1 and D1 and enhanced cyclin-dependent kinase inhibitor (CDKI) expression (17).
In animal models of colorectal cancer, suppression of disease activity was attributed to peroxisome proliferator-activated receptor gamma (PPARy) activation (36). Other possible mechanisms include increased apoptosis and enhanced caspase-3 activity in the colon mucosa (37). Preliminary studies in human breast cancers suggest anticancer effects occurred through suppression of fatty acid synthesis (39). In rectal cancer, CLA supplementation may improve markers of inflammation, and reduce angiogenesis and tumor invasion via matrix metalloproteinase-9 inhibition (38) (44).
Severe migraine aura with visual disturbance: In an older adult man without prior migraine history, and related to several separate occasions of CLA supplement ingestion as the trigger (56).
Reversible cerebral vasoconstriction syndrome: In a 50-year-old black woman who presented with a thunderclap headache less than 1 week after starting an herbal supplement weight loss containing CLA, green tea, and L-carnitine (57).