Efficacy of repeated phlebotomies in hypertriglyceridemia and iron overload: A prospective, randomized, controlled trial

Abstract

Background: High ferritin concentration is associated with hypertriglyceridemia, although it is not elucidated if iron overload has a causal role.

Objective: To evaluate the efficacy of repeated phlebotomies in patients with iron overload and hypertriglyceridemia.

Methods: Twelve weeks, 1:1 randomized, parallel-groups trial conducted at a University Hospital Lipid Clinic, including 86 subjects aged 18-70 years with serum ferritin >300 ng/mL in men or >200 ng/mL in women and triglycerides >200 mg/dL. Participants underwent: (1) three phlebotomies (every 3 weeks) and lipid-lowering dietary counseling or (2) lipid-lowering dietary counseling. The main outcome measured was the mean difference in percent change in triglyceride concentration between groups after the intervention. The mean differences in percent change of other clinical and biochemical variables (including cytokines and proinflammatory markers) after the intervention were also evaluated.

Results: Subjects who received phlebotomies showed a significant improvement in iron metabolism. The mean percent change in triglycerides between groups was -4.68 [-20.8, 11.4]%, P = .721. Retinol-binding protein 4 decreased by 9.98 ± 21.7% after phlebotomies, with a mean percent change between groups of -14.2 [-25.8, -2.73]%, P = .017, and correlated to gamma glutamyl transferase, alanine aminotransferase and aspartate aminotransferase change. Subjects with a large reduction in hepcidin showed a large improvement in liver enzymes and proinflammatory markers.

Conclusions: A lipid-lowering diet plus a substantial reduction in iron deposits with repeated phlebotomies in subjects with hyperferritinemia and hypertriglyceridemia did not reduce triglyceride concentration in comparison with a lipid-lowering diet. Iron depletion for lipid management in these patients is not supported.

Trial registration: ClinicalTrials.gov NCT02526121.

Keywords: Clinical trial; Ferritin; Hypertriglyceridemia; Iron overload; Phlebotomy.