Higher n-3 fatty acids are associated with more intense fenfluramine-induced ACTH and cortisol responses among cocaine-abusing men

Abstract

Preclinical studies have shown that diets supplemented with or deficient in n-3 polyunsaturated fatty acids (PUFAs) could influence serotonergic neurotransmission, but information about their effects on the serotonergic function of humans is scant. Therefore, simultaneous assessments of n-3 PUFAs and of the adrenocorticotropic hormone (ACTH) and cortisol responses to challenges with the serotonin (5-HT) probe d,l-fenfluramine (FEN) were performed in 25 cocaine-abusing men and 12 control subjects. Cocaine abusers were tested 18 days after their admission to a closed ward. ACTH and cortisol were measured in plasma samples collected on two testing days separated by 48 h following the random administration of 60 mg of FEN or placebo. Fatty acids were measured in the first test day samples. Patients' FEN-induced ACTH rises were significantly and positively correlated with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Patients' cortisol rises were positively and significantly correlated with EPA but not with DHA. There were no significant correlations between hormonal responses and pre-hospitalization cocaine use parameters. Control subjects' responses to FEN were not correlated with any PUFA. In conclusion, higher EPA and DHA levels were associated with a more intense FEN-induced ACTH response and higher EPA levels with a more intense cortisol response in cocaine-abusing men withdrawn from cocaine but not in control subjects. These findings support and expand existing evidence that EPA and DHA could influence 5-HT function in some human subgroups.

Figure 1

Patients’ partial regression plots of ACTH and cortisol responses (ΔΔs) to fenfluramine as a function of some PUFA values, using age as a control variable. PUFA values are expressed as % of total FAs. Regression lines, partial correlation coefficients (r) and their levels of significance are shown in each plot. Correlations are positive for total n-3 PUFAs, EPA and DHA. They are negative for the n-6/n-3 PUFA ratio.