Conjugated Linoleic Acid

Common Names

How It Works

Conjugated Linoleic Acid (CLA) has been shown to reduce cholesterol levels. Preliminary studies in humans suggest potential anticancer effects.

CLA is commonly found in dairy products and beef, and is made by microbes that live within the gut of certain animals. It is found throughout the body and may regulate cholesterol levels and help disrupt cancer cell replication. Although CLA is marketed as a weight loss product, studies show mixed results.
Purported Uses
- To prevent and treat cancer
  Animal studies have shown that CLA has antioxidant properties and may reduce the spread of cancer. Preliminary studies in humans suggest potential anticancer effects. However, clinical trials to confirm safety and effectiveness are needed.
- To treat high cholesterol
  Studies show that while CLA reduces total cholesterol levels, it also reduces 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 / caused insulin resistance.
Do Not Take If

You are taking blood-thinning drugs (eg, warfarin): CLA may increase the effects of anticoagulant and antiplatelet drugs, increasing the risk of bleeding.

You have diabetes: In obese men, CLA has caused insulin resistance and may increase blood glucose levels.

You have heart disease: In patients at risk for cardiovascular complications, it may increase processes that cause cell damage.
Side Effects
- Fatigue
- Gastrointestinal symptoms
Scientific Name

cis-9,trans-11 conjugated linoleic acid; trans-10,cis-12 conjugated linoleic acid
Clinical Summary

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 anti-carcinogenic effects more likely attributable to cis-9,trans-11 and anti-obesity effects attributable to the trans-10,cis-12 ⁽²³⁾ isomer.

In humans, studies of potential benefits of CLA are mixed. CLA supplemenation may have antithrombotic or antiatherosclerotic effects ⁽²⁴⁾. However, in obese men at high risk for cardiovascular disease, cis-9,trans-11 CLA supplementation decreased insulin sensitivity ⁽²⁵⁾. Another study suggests no significant effects on antioxidant metabolism in healthy overweight/obese individuals ⁽²⁶⁾. CLA may ameliorate inflammatory bowel disease ⁽²⁰⁾ and improve airway hyperreactivity in asthmatic individuals ⁽²¹⁾. Short-term high CLA intake did not affect blood pressure regulation ⁽²⁷⁾.

Data from studies on CLA-induced changes in body composition and weight reduction are also mixed. Some studies yielded positive results ⁽²⁸⁾ ⁽²⁹⁾ ⁽³⁰⁾ while others do not show benefits ⁽³¹⁾ ⁽³²⁾ ⁽⁴⁶⁾. Several double-blind RCTs have evaluated whether CLA can have additional effects on exercise performance. One study did not find any impact of CLA on aerobic capacity ⁽³³⁾, and another determined that CLA did not improve aerobically-induced neuromuscular fatigue ⁽³⁴⁾. However, CLA was shown to have triacylglycerol-lowering effects both on its own ⁽²²⁾ and along with aerobic exercise ⁽³⁵⁾, although it did not have any effect on other lipoprotein risk factors ⁽²²⁾.

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. More studies in the context of clinical trials are needed.

Reported adverse events include minor gastrointestinal symptoms ⁽⁹⁾ and severe fatigue ⁽⁶⁾.
Food Sources

Meat and dairy products
Purported Uses
- Cancer prevention
- High cholesterol
- Weight maintenance
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 anti-carcinogenic effects more likely attributable to cis-9,trans-11 and anti-obesity 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⁾.

The cis-9,trans-11 isomer may modify platelet activation and aggregation, and displayed anticoagulant properties ⁽²⁴⁾.
Contraindications

CLA should be used with caution in patients who have cardiovascular disease or diabetes, as it has increased lipid peroxidation and caused insulin resistance / decreased insulin sensitivity ⁽⁹⁾ ⁽²⁵⁾ ⁽⁴⁵⁾.
Adverse Reactions

Fatigue, gastrointestinal symptoms ⁽⁶⁾ ⁽⁹⁾.
Herb-Drug Interactions

Anticoagulant/antiplatelet drugs: The cis-9,trans-11 isomer has also been shown to have anticoagulant/antiplatelet activities ⁽²⁴⁾. It may increase the effect of drugs with similar properties.
References
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