Background and Aims Elevated hepatic de novo lipogenesis (DNL) is a key distinguishing characteristic of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. In rodent models of NAFLD, treatment with a surrogate of TVB‐2640, a pharmacological fatty acid synthase inhibitor, has been shown to reduce hepatic fat and other biomarkers of DNL. The purpose of this phase I clinical study was to test the effect of the TVB‐2640 in obese men with certain metabolic abnormalities that put them at risk for NAFLD. Approach and Results Twelve subjects (mean ± SEM, 42 ± 2 years, body mass index 37.4 ± 1.2 kg/m2, glucose 103 ± 2 mg/dL, triacylglycerols 196 ± 27 mg/dL, and elevated liver enzymes) underwent 10 days of treatment with TVB‐2640 at doses ranging from 50‐150 mg/day. Food intake was controlled throughout the study. Hepatic DNL was measured before and after an oral fructose/glucose bolus using isotopic labeling with 1‐13C1‐acetate intravenous infusion, followed by measurement of labeled very low‐density lipoprotein palmitate via gas chromatography mass spectometry. Substrate oxidation was measured by indirect calorimetry. Across the range of doses, fasting DNL was reduced by up to 90% (P = 0.003). Increasing plasma concentrations of TVB‐2640 were associated with progressive reductions in the percent of fructose‐stimulated peak fractional DNL (R2 = −0.749, P = 0.0003) and absolute DNL area under the curve 6 hours following fructose/glucose bolus (R2 = −0.554, P = 0.005). For all subjects combined, alanine aminotransferase was reduced by 15.8 ± 8.4% (P = 0.05). Substrate oxidation was unchanged, and safety monitoring revealed that the drug was well tolerated, without an increase in plasma triglycerides. Alopecia occurred in 2 subjects (reversed after stopping the drug), but otherwise no changes were observed in fasting glucose, insulin, ketones, and renal function. Conclusion These data support the therapeutic potential of a fatty acid synthase inhibitor, TVB‐2640 in particular, in patients with NAFLD and nonalcoholic steatohepatitis.

The present investigation was undertaken to assess the efficacy of oral iron supplementation during pregnancy by using a gastric delivery system (GDS). Three hundred seventy-six pregnant women between 16 and 35 y of age and 14 and 22 wk gestation were selected if mild anemia was present (hemoglobin concentration 80-110 g/L). The participants were randomly assigned to one of three study groups given no iron, two FeSO4 tablets (100 mg Fe) daily, or one GDS capsule (50 mg Fe) daily. Blood was obtained initially and after 6 and 12 wk for measurement of red blood cell and iron indexes, including serum transferrin receptor. There was a significant and comparable improvement in hematologic and iron-status measurements in the two groups of women given iron whereas iron deficiency evolved in women given no iron supplement. We conclude that by eliminating gastrointestinal side effects and reducing the administration frequency of an iron supplement to once daily, a GDS offers significant advantages for iron supplementation of pregnant women.