CLA 1250 [Discontinued] by MRM

POSSIBLY EFFECTIVE

• Hypertension. Oral CLA seems to modestly reduce blood pressure when used along with ramipril. However, oral CLA alone does not seem to reduce blood pressure. Details: A meta-analysis of small clinical trials shows that taking CLA in doses of 1 gram to 10.8 grams daily does not lower systolic or diastolic blood pressure when compared with placebo or a control diet (111053). However, this analysis is limited by the heterogeneous populations in the individual studies. Only one study was specifically conducted in individuals with hypertension (45569). This small clinical trial in individuals with stage one uncontrolled hypertension shows that taking CLA 4.5 grams daily along with ramipril 37.5 mg daily for 8 weeks modestly reduces systolic and diastolic blood pressure when compared with ramipril alone (45569).
• Obesity. In adults and children, oral CLA seems to decrease fat mass by a small amount, including abdominal fat mass. However, it is unclear if oral CLA is beneficial for weight loss, body mass index (BMI) reduction, or improvement of metabolic measures. Details: Taking CLA 3-6.8 grams daily seems to decrease body fat mass, increase lean body mass, and reduce waist and hip circumference in some patients (2819,3153,4947,13137,45295,45303,45685,45799,97003,105809). A meta-analysis of clinical research in adults with overweight or obesity also undergoing an exercise program shows a small effect on body fat reduction, but not body weight or plasma lipids (111056). Most research suggests that doses greater than 3.4 grams daily do not seem to offer any additional benefit when compared with lower doses (2819,2821,3153,4947,10410,11327,13137,45295,45799). Also, supplementing milk with CLA 3 grams daily seems to reduce total fat mass in individuals with overweight when compared with placebo (45331). CLA also seems to reduce hunger and improve satiety and feelings of fullness, but this appetite suppression does not necessarily result in a lower energy intake or improved body weight maintenance (11327). In children with overweight aged 6-10 years, taking CLA 3 grams daily for approximately 7 months seems to reduce body fat, abdominal fat, and peripheral fat percentages when compared with placebo (45713). There is inconsistent evidence regarding the effects of CLA on body weight and BMI, with most research suggesting that CLA does not reduce total body weight or BMI (2819,2821,3153,10410,13137,45007,45679,45790,97003,97006). Also, taking CLA in combination with omega-3 fatty acids or chromium picolinate does not seem to improve BMI and body weight in individuals with overweight or obesity (42627,45431). Although one meta-analysis of clinical research shows that taking CLA 2.4-6 grams daily for 6-12 months increases weight loss by 0.7 kg and fat loss by 1.3 kg when compared with placebo, this effect is small and may not be clinically significant (91585). Also, taking CLA 3.4 grams daily for 1 year does not seem to prevent weight or body fat regain in individuals with overweight who previously lost some of their initial body weight (45083,45221). However, one study shows that taking CLA 8 grams daily for 16 weeks seems to reduce BMI in obese, postmenopausal adults with type 2 diabetes (45614). Some studies have evaluated the consumption of CLA-enriched fatty foods. In males with overweight, consuming butter enriched with CLA does not seem to have beneficial metabolic effects (45192). Also, in individuals with overweight or obesity, consuming a goat cheese naturally enriched in CLA and omega-3 fatty acids for 12 weeks does not seem to improve BMI, fat mass, or weight, or most metabolic measures, including fasting glucose, blood pressure, or inflammatory factors, when compared to a control goat cheese. However, there was an increase in total cholesterol, possibly related to an increase in high-density lipoprotein (HDL) cholesterol, and reduced levels of C-reactive protein (CRP) (105808). There is evidence that the isolated trans-10,cis-12 isomer of CLA can increase hyperproinsulinemia and insulin resistance in patients with abdominal obesity (2821,13026,13137). Hyperproinsulinemia is an independent risk factor for type 2 diabetes and cardiovascular disease. Therefore, CLA might not be a good choice for obese patients. However, most commercial CLA products contain a mixture of CLA isomers. It is not known if these mixed CLA isomer products carry this risk. One meta-analysis of clinical research shows that insulin resistance is modestly reduced when a CLA supplement is taken by adults undergoing an exercise program when compared with exercise alone (111056).

POSSIBLY INEFFECTIVE

• Common cold. Oral CLA does not seem to be beneficial for common cold prevention or treatment. Details: Some clinical research shows that taking CLA 2 grams daily does not reduce the risk of developing a cold or reduce cough or sore throat severity in individuals with a common cold when compared with placebo (45577).
• Diabetes. Oral CLA does not seem to be beneficial for diabetes. Details: Some clinical research shows that taking CLA 6.4 grams daily for 16 weeks does not improve fasting glucose, postprandial glucose, or insulin in individuals with type 2 diabetes when compared with safflower oil (45614,45835).
• Hyperlipidemia. Oral CLA does not seem to be beneficial for hyperlipidemia. Details: A meta-analysis and individual clinical trials show that taking CLA as supplements or fortified foods does not improve levels of cholesterol or triglycerides (45790,97006,111054). One meta-analysis of small clinical trials in heterogenous populations shows that taking CLA does not improve levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglycerides, and modestly DECREASES levels of high-density lipoprotein (HDL) cholesterol, when compared with taking placebo or a control diet (111054). CLA has generally been taken in doses of 1.4 to 6.8 grams daily for up to 24 weeks (45790,97006,111054). However, research in patients with hyperlipidemia is limited. Most studies have included general populations of healthy adults, patient with type 2 diabetes, or populations with obesity.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). It is unclear if oral CLA is beneficial for reducing symptoms of allergic rhinitis. Details: Clinical research shows that taking CLA 2 grams daily for 12 weeks improves overall well-being in patients with birch pollen allergy when compared with placebo, but does not improve eye or total allergy symptoms (45395).
• Asthma. It is unclear if oral CLA is beneficial for reducing symptoms of asthma. Details: A small clinical trial in patients with mild asthma shows that taking CLA 4.5 grams daily for 12 weeks improves airway hypersensitivity and tolerance to strenuous exercise when compared with placebo, but without significantly reducing the need to use rescue bronchodilators or improving lung capacity (45787). In addition, a small clinical trial in children 6-18 years of age with allergic asthma shows that taking CLA 3 grams daily for 12 weeks does not reduce the use of emergency bronchodilators or improve peak expiratory flow, forced expiratory volume (FEV1), or vital lung capacity when compared with placebo (97005).
• Atherosclerosis. Although there is interest in using oral CLA for preventing atherosclerosis, there is insufficient reliable information about the clinical effects of CLA for this purpose.
• Athletic performance. It is unclear if oral CLA is beneficial for improving athletic performance. Details: Some preliminary clinical research in student athletes shows that taking CLA powder (CLAce Powder, The Nisshin OilliO Group, Ltd.) 900 mg daily for 14 days increases time to exhaustion during exercise by an average of 179 seconds, but does not reduce rate of perceived exertion, when compared with placebo (97002). Other small clinical trials show that taking a specific product containing CLA oil (Clarinol A-80, Stepan Specialty Products, LLC) 5.63 grams daily for 6 weeks in combination with aerobic training does not improve muscle endurance, muscle power, peak oxygen uptake, or cardiorespiratory fatigue threshold when compared with placebo in untrained to moderately trained males (91587,91588).
• Breast cancer. It is unclear if dietary CLA is beneficial for preventing breast cancer. Details: Some observational research has found that a higher intake of CLA in foods, particularly cheese, is linked with a lower risk of developing breast cancer in postmenopausal individuals (5058). However, other population research has found that intake of CLA is not associated with a reduced risk of breast cancer (45609). Furthermore, some epidemiological evidence has found that CLA intake might be weakly associated with an increased risk of breast cancer (45048).
• Cognitive function. It is unclear if oral CLA is beneficial for improving cognitive function in older adults. Details: Preliminary clinical research in older adults shows that taking CLA 1.75 grams twice daily for 6 weeks may modestly improve verbal learning and recall in males, but not females, when compared with placebo (97008).
• Colorectal cancer. It is unclear if dietary CLA is beneficial for preventing colorectal cancer. Details: Epidemiological research has found that high dietary intake of CLA might reduce the risk of colorectal cancer in females by up to 39% (13775). It is not known if taking CLA supplements is associated with a reduced risk of colorectal cancer.
• Metabolic syndrome. It is unclear if oral CLA is beneficial for metabolic syndrome. Details: Evidence from a small clinical trial shows that taking CLA 3 grams daily orally for 90 days, along with a hypocaloric diet, decreases body fat mass by approximately 3% when compared to baseline in females with metabolic syndrome. However, this reduction does not appear to be significant when compared with placebo treatment, and CLA does not lower blood lipid levels or blood pressure (91586).
• Muscle strength. It is unclear if oral CLA is beneficial for increasing muscle strength. Details: Some preliminary clinical research shows that adding CLA 6 grams to supplementation with creatine 9 grams and whey protein 36 grams daily for 12 weeks modestly enhances strength improvement and lean tissue mass when compared with placebo in adults participating in strength training (45596). However, other clinical research shows that taking CLA 5 grams daily for 7 weeks does not improve most measures of strength in adults participating in resistance training when compared with placebo, although bench press strength was modestly improved in males, and lean tissue mass and fat mass were also improved (45222). Other clinical research shows that taking CLA 6 grams daily for 4 weeks does not improve body composition or strength in resistance-trained athletes (45041). The reasons for these discrepancies are unclear, but may be related to the duration of treatment.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral CLA is beneficial for NAFLD. Details: Preliminary clinical research shows that taking CLA (Nutrifit, Nutricentury) 1 gram three times daily in conjunction with a weight loss diet for 8 weeks reduces fat mass, low-density lipoprotein (LDL) cholesterol levels, and alanine aminotransferase (ALT) levels and increases muscle mass when compared with a weight loss diet alone in obese adults with NAFLD. CLA was also associated with a reduction in glycated hemoglobin, but with no corresponding reduction in fasting plasma glucose (97004).
• Physical performance. It is unclear if oral CLA is beneficial for improving physical performance in older adults. Details: Preliminary clinical research in adults 65-85 years of age shows that taking CLA 1.75 grams twice daily for 6 weeks does not improve handgrip strength or hand discomfort when compared with placebo (97008).
• Rheumatoid arthritis (RA). It is unclear if oral CLA is beneficial for RA. Details: Preliminary clinical research shows that taking CLA 2.5 grams daily with or without vitamin E 400 mg daily for 12 weeks reduces pain and morning stiffness and reduces erythrocyte sedimentation rate in patients with RA when compared to baseline (45730). The validity of these findings is limited by the lack of a comparator group. More evidence is needed to rate conjugated linoleic acid for these uses.

(Read more about CONJUGATED LINOLEIC ACID (CLA))

LIKELY SAFE ...when used orally in amounts found in foods. CLA occurs naturally in milk fat, beef, and the meat of other ruminant animals (5924,5925,5932,5933).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts of up to 6. 8 grams daily, short-term (2819,2821,3153,4947,10410,11327,111056).

CHILDREN: LIKELY SAFE
when used orally in amounts found in foods. CLA occurs naturally in milk fat, beef, and the meat of other ruminant animals (5924,5925,5932,5933).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in medicinal amounts. Some evidence suggests that CLA 3 grams daily can be taken safely for up to 7 months (45713).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts found in foods (5924,5932,5933). There is insufficient reliable information available about the safety of CLA when used in medicinal amounts during pregnancy or lactation; avoid using.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, CLA may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Some clinical evidence suggests that intake of CLA reduces platelet aggregation by approximately 10% (45607). The clinical significance of this effect is unclear.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = A Theoretically, taking CLA with antihypertensive drugs might increase the risk of hypotension.  Details Animal research suggests that a particular form of CLA reduces systolic blood pressure (45081). Also, some clinical research shows that CLA enhances the blood pressure-lowering effects of ramipril, an antihypertensive drug (45569).

RAMIPRIL (ALTACE) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = A Theoretically, taking black seed with ramipril might increase the risk of hypotension.  Details Some clinical research shows that CLA enhances the blood pressure-lowering effects of ramipril (45569).

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General ...Orally, CLA is well tolerated when found in foods. When taken in medicinal amounts, CLA seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, flatulence, loose stools, and nausea.
Serious Adverse Effects (Rare) :
Orally: Cases of hepatotoxicity have been reported.

Cardiovascular ...Some preliminary clinical research suggests that the t10,c12 isomer of CLA can decrease high-density lipoprotein (HDL) cholesterol levels (2821). This isomer of CLA, as well as a mixture of CLA isomers, seems to increase plasma triglyceride levels, the ratio of low-density lipoprotein (LDL) cholesterol to HDL cholesterol, and the ratio of total cholesterol to HDL cholesterol (45148,45468), although not all research has identified these effects (107475).
A meta-analysis of 6 randomized, controlled trials shows that administration of CLA in individuals who are overweight or obese significantly increases lipoprotein (a) levels, a value associated with increased risk of cardiovascular disease. Subgroup analyses suggest this increase is more prominent in trials that are longer than 6 months in duration and with CLA doses of at least 3.5 grams daily (107475).

Endocrine ...Orally, CLA has been shown to increase insulin resistance and glucose concentrations, as well as decrease insulin sensitivity in some patients, including obese individuals or patients with type 2 diabetes (2821,13026,45145,45152,45513). Some evidence suggests that this effect is isomer-specific and occurs with only the t10,c12 isomer (2821,13026), while other evidence shows that decreased insulin sensitivity may also occur with the c9,t11 isomer or with a 50:50 mixture of c9,t11 and t10,c12 isomers (45145,45152).

Gastrointestinal ...Orally, the most common adverse effect reported with CLA is gastrointestinal upset including diarrhea, constipation, nausea, loose stools, dyspepsia, bloating, and flatulence (3153,4947,45280,45705,45730,111056). Esophageal irritation was reported in one patient who bit open and swallowed a capsule containing CLA (45577).

Hepatic ...Orally, clinical research shows that CLA 3 grams daily for 12 weeks does not affect liver outcome measures (105809). However, there are at least two case reports of hepatotoxicity. Asthenia, jaundice, and pruritus were reported in a 46-year-old female who consumed CLA for two weeks. Abnormal liver enzyme levels returned to normal following discontinuation of CLA supplementation (45483). Hepatotoxicity, presenting as fulminant hepatitis and characterized by anorexia, nausea, jaundice, choluria, and hepatic encephalopathy requiring liver transplantation has also been reported in a 63-year-old female taking a CLA-containing weight-loss supplement for one month (91589).

Musculoskeletal ...Orally, CLA has been reported to cause back ache in one individual in one clinical trial (45787).

Neurologic/CNS ...Orally, CLA may cause headache or fatigue (3153,45787). In one case report, a 50-year-old female presented with headache and subarachnoid hemorrhage due to reversible cerebral vasoconstriction syndrome (RCVS) after taking a combination product containing green tea, L-carnitine, and CLA for one week. At 28 days after discontinuation of the combination product and surgery, angiography showed complete regression of vascular restrictions (97007). It is unclear if this adverse effect was due to CLA, another ingredient in the product, or a combination of ingredients.

Other ...Orally, CLA has been reported to cause halitosis in one patient in one clinical trial (45839).

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