Ketones can reactivate the production of
fetal hemoglobin (HbF) in vitro and in vivo. A reactivation of HbF by
ketones, which are generated during
starvation, remains largely speculative. Therefore, we investigated HbF in 31 women with
anorexia nervosa or
bulimia, using both of these as models of intermittent
starvation ketosis. For comparison, we also studied 42 female control subjects matched for age.
beta-Hydroxybutyrate levels were higher in patients than in controls (460 +/- 90 v 110 +/- 20 mumol/L; P < .0001). We correlated
beta-hydroxybutyrate, metabolic, and hematologic parameters with HbF. HbF was measured with high pressure liquid chromatography. The data were analyzed with logistic regression analysis. An elevated HbF fraction (> 0.87%) was observed four times as often in patients than in controls (29% v 7%, P = .01). After adjustment for age, we found HbF elevations associated with
beta-hydroxybutyrate levels (P = .005). No other correlations between the various metabolic/ hematologic parameters and HbF were significant. In conclusion,
beta-hydroxybutyrate generated in
starvation is associated with increased levels of HbF. Thus, unrestrained lipolysis can produce
beta-hydroxybutyrate in sufficient quantities to induce a clinically measurable amount of HbF. These findings suggest that intermittent
ketosis might also explain some increases of HbF in
type 1 diabetes and pregnancy.