Effects of phlebotomy-induced reduction of body iron stores on metabolic syndrome: results from a randomized clinical trial.
BACKGROUND
Metabolic syndrome (METS) is an increasingly prevalent but poorly understood clinical condition characterized by insulin resistance, glucose intolerance, dyslipidemia, hypertension, and obesity. Increased oxidative stress catalyzed by accumulation of iron in excess of physiologic requirements has been implicated in the pathogenesis of METS, but the relationships between cause and effect remain uncertain. We tested the hypothesis that phlebotomy-induced reduction of body iron stores would alter the clinical presentation of METS, using a randomized trial.


METHODS
In a randomized, controlled, single-blind clinical trial, 64 patients with METS were randomly assigned to iron reduction by phlebotomy (n = 33) or to a control group (n = 31), which was offered phlebotomy at the end of the study (waiting-list design). The iron-reduction patients had 300 ml of blood removed at entry and between 250 and 500 ml removed after 4 weeks, depending on ferritin levels at study entry. Primary outcomes were change in systolic blood pressure (SBP) and insulin sensitivity as measured by Homeostatic Model Assessment (HOMA) index after 6 weeks. Secondary outcomes included HbA1c, plasma glucose, blood lipids, and heart rate (HR).


RESULTS
SBP decreased from 148.5 ± 12.3 mmHg to 130.5 ± 11.8 mmHg in the phlebotomy group, and from 144.7 ± 14.4 mmHg to 143.8 ± 11.9 mmHg in the control group (difference -16.6 mmHg; 95% CI -20.7 to -12.5; P < 0.001). No significant effect on HOMA index was seen. With regard to secondary outcomes, blood glucose, HbA1c, low-density lipoprotein/high-density lipoprotein ratio, and HR were significantly decreased by phlebotomy. Changes in BP and HOMA index correlated with ferritin reduction.


CONCLUSIONS
In patients with METS, phlebotomy, with consecutive reduction of body iron stores, lowered BP and resulted in improvements in markers of cardiovascular risk and glycemic control. Blood donation may have beneficial effects for blood donors with METS.


BACKGROUND
ClinicalTrials.gov: NCT01328210 Please see related article: http://www.biomedcentral.com/1741-7015/10/53.
Department of Internal Medicine, Kliniken Essen-Mitte, University Duisburg-Essen, Essen, Germany.
Khosrow S
KS
Houschyar
Rainer
R
Lüdtke
Gustav J
GJ
Dobos
Ulrich
U
Kalus
Martina
M
Broecker-Preuss
Thomas
T
Rampp
Benno
B
Brinkhaus
Andreas
A
Michalsen
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000502:physiology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006339:Heart Rate / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D007501:Iron / Q000097:blood*; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology* / Q000628:therapy*; D008875:Middle Aged; D018962:Phlebotomy; D016896:Treatment Outcome
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007501:Iron; D008055:Lipids; C517652:hemoglobin A1c protein, human