Overweight volunteers who took 4.5 grams of CLA per day for one year had an increase in their blood levels of lipoprotein(a), a risk factor for heart disease.⁷ In a double-blind study of human volunteers, supplementation with 4.2 grams per day of a mixture of cis-9,trans-11 CLA and trans-10,cis-12 CLA for three months increased the concentration of C-reactive protein, another risk factor for heart disease.⁸ In a study of healthy volunteers, supplementing with 4.5 grams of CLA per day for 12 weeks caused an impairment of blood vessel function (endothelial dysfunction), which is believed to be associated with an increased risk of heart disease.⁹ Taken together, these findings suggest that long-term use of CLA could increase the risk of developing heart disease.

In a double-blind study of people with type 2 diabetes, supplementing with 3 grams of CLA per day for eight weeks significantly increased blood glucose levels by 6.3% and decreased insulin sensitivity.¹⁰ A reduction in insulin sensitivity was also seen in a study of overweight men without diabetes after treatment with 3 grams of CLA per day for three months.¹¹ However, in another study of obese men and women, supplementation with 6 grams of CLA per day for 24 weeks had no significant effect on blood glucose levels or insulin sensitivity.¹² Moreover, in a study of young sedentary men, 4 grams of CLA per day for eight weeks improved insulin sensitivity.¹³ Although the studies are conflicting, it would be prudent for people who have, or are at risk of developing, diabetes to monitor their blood sugar levels during long-term use of CLA. One unpublished human trial reported isolated cases of gastrointestinal upset.¹⁴