Association Between Plasma Caffeine and Other Methylxanthines and Metabolic Parameters in a Psychiatric Population Treated With Psychotropic Drugs Inducing Metabolic Disturbances

Abstract

Importance: Multiple studies conducted in the general population identified an association between self-reported coffee consumption and plasma lipid levels. To date, no study assessed whether and which plasma methylxanthines (caffeine and/or its metabolites, i.e., paraxanthine, theophylline, and theobromine) are associated with plasma lipids. In psychiatric patients, an important coffee consumption is often reported and many psychotropic drugs can induce a rapid and substantial increase of plasma lipid levels. Objective: To determine whether plasma methylxanthines are associated with metabolic parameters in psychiatric patients receiving treatments known to induce metabolic disturbances. Design, Setting, and Participants: Data were obtained from a prospective study including 630 patients with metabolic parameters [i.e., body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and fasting triglycerides (TG)] monitored routinely during psychotropic treatment. Exposures: Plasma methylxanthines levels. Main Outcomes and Measures: Metabolic variables including BMI and plasma lipid levels. Results: Multivariate analyses indicated that BMI, TC, HDL-C, and non-HDL-C increased significantly with increasing total methylxanthines (p _corrected ≤ 0.05). In addition, compared to patients with plasma caffeine concentration in the lowest quartile, those with caffeine concentration in the highest quartile were twice more prone to suffer from non-HDL hypercholesterolemia (p _corrected = 0.05), five times more likely to suffer from hypertriglyceridemia (p _corrected = 0.01) and four times more susceptible to be overweight (p _corrected = 0.01). Conclusions and Relevance: This study showed that plasma caffeine and other methylxanthines are associated with worsening of metabolic parameters in patients receiving psychotropic treatments known to induce metabolic disturbances. It emphasizes that important caffeine consumption could be considered as an additional environmental risk factor for metabolic worsening in patients receiving such treatments.

Keywords: lipids; metabolic parameters; plasma caffeine level; plasma methylxanthines; psychotropic drugs; secondary effects.

Figure 1

(A) Odds ratio of non-HDL hypercholesterolemia (i.e., abnormal levels of plasma non-HDL cholesterol) by quartiles of plasma methylxanthines. Quartile 1 was considered as the reference. Odds ratio were adjusted for age, sex, smoking status, psychotropic medication, treatment duration and BMI. 95 CI: 95% confidence interval. 90 CI: 90% confidence interval. White diamonds represent estimates of adjusted odd ratio. Log caffeine: Q1: ≤ 4.43 ng/ml; Q2: >4.43– ≤ 6.03 ng/ml; Q3: >6.03– ≤ 7.32 ng/ml; Q4: >7.32 ng/ml; Log paraxanthine: Q1: ≤ 5.1 ng/ml; Q2: >5.1– ≤ 6.23 ng/ml; Q3: >6.23– ≤ 7.07 ng/ml; >7.07 ng/ml; Log theophylline: Q1: ≤ 3.43 ng/ml; Q2: >3.43– ≤ 4.31 ng/ml; Q3: >4.31– ≤ 5.16 ng/ml; Q4: >5.16 ng/ml; Log theobromine: Q1: ≤ 5.55 ng/ml; Q2: >5.55– ≤ 6.44 ng/ml; Q3: >6.44– ≤ 7.17 ng/ml; Q4: >7.17 ng/ml; Log total methylxanthine: Q1: ≤ 6.69 ng/ml; Q2: >6.69– ≤ 7.6 ng/ml; Q3: >7.6– ≤ 8.34 ng/ml; Q4: >8.34 ng/ml. Non-HDL hypercholesterolemia was defined as plasma levels of total cholesterol ≥4 mmol/l, according to ESH/ESC guidelines. (B) Odds ratio of hypertriglyceridemia by quartiles of plasma methylxanthines. Quartile 1 was considered as the reference. Odds ratio (95% CI) were adjusted for age, sex, smoking status, psychotropic medication, treatment duration, and BMI. 95 CI: 95% confidence interval. 90 CI: 90% confidence interval. White diamonds represent estimates of adjusted odd ratio. Log caffeine: Q1: ≤ 4.43 ng/ml; Q2: >4.43– ≤ 6.03 ng/ml; Q3: >6.03– ≤ 7.32 ng/ml; Q4: >7.32 ng/ml; Log paraxanthine: Q1: ≤ 5.1 ng/ml; Q2: >5.1– ≤ 6.23 ng/ml; Q3: >6.23– ≤ 7.07 ng/ml; >7.07 ng/ml; Log theophylline: Q1: ≤ 3.43 ng/ml; Q2: >3.43– ≤ 4.31 ng/ml; Q3: >4.31– ≤ 5.16 ng/ml; Q4: >5.16 ng/ml; Log theobromine: Q1: ≤ 5.55 ng/ml; Q2: >5.55– ≤ 6.44 ng/ml; Q3: >6.44– ≤ 7.17 ng/ml; Q4: >7.17 ng/ml; Log total methylxanthine: Q1: ≤ 6.69 ng/ml; Q2: >6.69– ≤ 7.6 ng/ml; Q3: >7.6– ≤ 8.34 ng/ml; Q4: >8.34 ng/ml. Hypertriglyceridemia was defined as plasma levels of triglyceride ≥2 mmol/l, according to ESH/ESC guidelines. Only patients in fasting conditions were considered in these analyses. (C) Odds ratio of overweight by quartiles of plasma methylxanthines. Quartile 1 was considered as the reference. Odds ratio (95% CI) were adjusted for age, sex, smoking status, psychotropic medication, treatment duration and total cholesterol levels. 95 CI: 95% confidence interval. 90 CI: 90% confidence interval. White diamonds represent estimates of adjusted odd ratio. Log caffeine: Q1: ≤ 4.43 ng/ml; Q2: >4.43– ≤ 6.03 ng/ml; Q3: >6.03– ≤ 7.32 ng/ml; Q4: >7.32 ng/ml; Log paraxanthine: Q1: ≤ 5.1 ng/ml; Q2: >5.1– ≤ 6.23 ng/ml; Q3: >6.23– ≤ 7.07 ng/ml; >7.07 ng/ml; Log theophylline: Q1: ≤ 3.43 ng/ml; Q2: >3.43– ≤ 4.31 ng/ml; Q3: >4.31– ≤ 5.16 ng/ml; Q4: >5.16 ng/ml; Log theobromine: Q1: ≤ 5.55 ng/ml; Q2: >5.55– ≤ 6.44 ng/ml; Q3: >6.44– ≤ 7.17 ng/ml; Q4: >7.17 ng/ml; Log total methylxanthine: Q1: ≤ 6.69 ng/ml; Q2: >6.69– ≤ 7.6 ng/ml; Q3: >7.6– ≤ 8.34 ng/ml; Q4: >8.34 ng/ml. Overweight was defined as body mass index ≥25 kg/m².