Metabolic and hepatic effects of bloodletting in dysmetabolic iron overload syndrome: A randomized controlled study in 274 patients.
Study Goal
The researchers aimed to determine whether iron depletion via bloodletting combined with lifestyle and diet advice (LFDA) improves metabolic and hepatic outcomes, including alanine aminotransferase levels, in nondiabetic patients with dysmetabolic iron overload syndrome (DIOS).
Results Summary
The study found no significant improvement in alanine aminotransferase levels (33 ± 22 IU/L in the intervention group vs. 37 ± 21 IU/L in controls, P = 0.10) or other metabolic and hepatic markers with iron depletion. Weight loss, rather than bloodletting, was associated with improved outcomes.
Population
Nondiabetic DIOS patients with hepatic iron >50 μmol/g at MRI.
Effective Dosage
Not specified (bloodletting volume: 4.9 ± 1.6 L over the study period).
Duration
1 year.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
bloodletting associated with lifestyle and diet advice (LFDA) | decrease | ferritin levels | nondiabetic DIOS patients with hepatic iron >50 μmol/g | 71 ± 48 μg/L after removal of 4.9 ± 1.6 L of blood versus 733 ± 277 μg/L | showed | #1 |
bloodletting associated with lifestyle and diet advice (LFDA) | no change | glycemia | nondiabetic DIOS patients with hepatic iron >50 μmol/g | 5.44 ± 0.7 versus 5.49 ± 0.7 mmol/L | showed | #2 |
bloodletting associated with lifestyle and diet advice (LFDA) | increase | body weight | nondiabetic DIOS patients with hepatic iron >50 μmol/g | +0.5 ± 4.3% versus -0.6 ± 3.3% | showed | #3 |
bloodletting associated with lifestyle and diet advice (LFDA) | increase | homeostasis model of assessment of insulin resistance | nondiabetic DIOS patients with hepatic iron >50 μmol/g | 3.39 versus 2.40 | showed | #4 |
bloodletting associated with lifestyle and diet advice (LFDA) | no change | alanine aminotransaminase | nondiabetic DIOS patients with hepatic iron >50 μmol/g | 33 ± 22 versus 37 ± 21 IU/L | showed | #5 |
bloodletting associated with lifestyle and diet advice (LFDA) | no change | aspartate aminotransaminase | nondiabetic DIOS patients with hepatic iron >50 μmol/g | 27 ± 13 versus 27 ± 10 IU/L | showed | #6 |
bloodletting associated with lifestyle and diet advice (LFDA) | no change | gamma-glutamyl transferase | nondiabetic DIOS patients with hepatic iron >50 μmol/g | 54 ± 138 versus 49 ± 35 IU/L | showed | #7 |
bloodletting associated with lifestyle and diet advice (LFDA) | no change | Fatty Liver Index | nondiabetic DIOS patients with hepatic iron >50 μmol/g | 58.9 ± 24.6 versus 61.2 ± 22.9 | showed | #8 |
bloodletting associated with lifestyle and diet advice (LFDA) | no change | Fibrosis-4 score | nondiabetic DIOS patients with hepatic iron >50 μmol/g | 1.5 ± 0.6 versus 1.30 ± 0.6 | showed | #9 |
bloodletting associated with lifestyle and diet advice (LFDA) | increase | Fatigue | nondiabetic DIOS patients with hepatic iron >50 μmol/g | 25.3% of venesected patients versus 2.3% of controls | occurred in | #10 |
sustained modification of diet and lifestyle habits | neutral | first therapeutic intervention | DIOS patients | - | remains | #11 |
UNLABELLED: Dysmetabolic iron overload syndrome (DIOS) is a common cause of hyperferritinemia, accounting for a mild increase of iron stores in insulin-resistant subjects. Iron removal could improve insulin sensitivity. We performed a prospective, randomized, controlled trial (NCT01015525) in nondiabetic DIOS patients with hepatic iron >50 μmol/g at magnetic resonance imaging to compare the metabolic and hepatic outcomes of 1-year maintenance of serum ferritin levels <50 μg/L by bloodletting associated with lifestyle and diet advice (LFDA) to those of LFDA only. Patients were randomly assigned (1:1) with stratification by center (n = 8) and hyperglycemia (>5.6 mmol/L). Sample size was calculated to provide 90% power and a difference in fasting glycemia of 0.25 mmol/L. Analysis was done in an intention-to-treat population. In 2010-2014, 146 patients were randomly assigned to receive venesections with LFDA and 128 to LFDA only. At the end of the study, comparison of iron-depleted patients and controls showed ferritin levels 71 ± 48 μg/L after removal of 4.9 ± 1.6 L of blood versus 733 ± 277 μg/L (P < 0.0001), glycemia 5.44 ± 0.7 versus 5.49 ± 0.7 mmol/L (P = 0.57), body weight +0.5 ± 4.3% versus -0.6 ± 3.3% (P = 0.03), homeostasis model of assessment of insulin resistance 3.39 versus 2.40 (P = 0.002), alanine aminotransaminase 33 ± 22 versus 37 ± 21 IU/L (P = 0.10), aspartate aminotransaminase 27 ± 13 versus 27 ± 10 IU/L (P = 0.81), gamma-glutamyl transferase 54 ± 138 versus 49 ± 35 IU/L (P = 0.72), Fatty Liver Index 58.9 ± 24.6 versus 61.2 ± 22.9 (P = 0.37), and Fibrosis-4 score 1.5 ± 0.6 versus 1.30 ± 0.6 (P = 0.51). Fatigue occurred in 25.3% of venesected patients versus 2.3% of controls (P < 0.0001). In the subgroup of patients who lost weight, glycemia, homeostasis model of assessment of insulin resistance, serum ferritin, lipid profile, and liver function tests improved irrespective of bloodletting. CONCLUSION: In DIOS patients, iron depletion by bloodletting does not improve metabolic and hepatic features, is associated with weight gain, and is not as well tolerated as expected; sustained modification of diet and lifestyle habits remains the first therapeutic intervention in DIOS. (Hepatology 2017;65:465-474).