Effect of valproic acid on body weight, food intake, physical activity and hormones: results of a randomized controlled trial.
The objective of this study was to identify mechanisms through which valproic acid (VPA) causes weight gain. Healthy participants (N = 52) were randomized to VPA or placebo in a double-blind study. Energy intake (EI) was measured in the laboratory at lunch and dinner, and physical activity (PA) was measured with accelerometry. Glucose levels and hormones [Peptide YY(3-36), glucagon-like peptide-1 (GLP-1), leptin, ghrelin, insulin] that regulate EI were measured. Assessments occurred at baseline and week 3. Change from baseline was evaluated with mixed models (alpha = 0.05). Weight significantly increased in the VPA group (+0.49 kg), but not the placebo group. The VPA group increased fast food fats cravings and decreased glucose levels compared with placebo. Change in weight, EI and PA did not differ by group. Within group analyses indicated that the VPA group increased PA, hunger, binge eating, depression and GLP-1. VPA-associated weight gain is not likely due to changes in PA or the gut hormones studied. Although EI did not increase when measured after 3 weeks of treatment, VPA decreased glucose levels and increased motivation to eat; hence, EI might have increased in the short-term. Research testing VPA on short-term (1 week) EI, metabolism, and substrate partitioning is warranted.
Martin
C K
CK
Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA. corby.martin@pbrc.edu
Han
H
H
Anton
S D
SD
Greenway
F L
FL
Smith
S R
SR
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D001290:Attitude; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects*; D003404:Creatinine / Q000097:blood; D003692:Delayed-Action Preparations; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D054439:Ghrelin / Q000097:blood*; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects*; D010349:Patient Compliance; D010446:Peptide Fragments; D019894:Peptide YY / Q000097:blood*; D012709:Serum Albumin / Q000187:drug effects; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*
D000927:Anticonvulsants; D001786:Blood Glucose; D003692:Delayed-Action Preparations; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D008055:Lipids; D010446:Peptide Fragments; D012709:Serum Albumin; D019894:Peptide YY; C061785:peptide YY (3-36); D014635:Valproic Acid; D052216:Glucagon-Like Peptide 1; D003404:Creatinine